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Background: Neoadjuvant chemoradiation (CRT) impairs bowel function in patients with rectal cancer treated with total mesorectal excision (TME). The impact of other forms of neoadjuvant therapy such as neoadjuvant chemotherapy alone (NC) and induction chemotherapy followed by CRT (total neoadjuvant therapy or TNT) on postoperative bowel function has not been investigated.Methods: We conducted a retrospective review of 176 rectal cancer patients treated between November 1, 2011, and August 31, 2017. All patients completed the MSKCC Bowel Function Instrument (BFI), a validated bowel function questionnaire, at least 6 months after TME and/or ileostomy reversal. Differences in BFI scores were compared across four groups (surgery alone, CRT, NC, and TNT) and also according to exposure to neoadjuvant RT and neoadjuvant chemotherapy. A multivariable linear regression model was used to evaluate the independent relationship between exposure to neoadjuvant RT or chemotherapy and BFI.Results: BFI total scores were significantly different between the four groups (p = 0.008). Exposure to RT correlated with worse BFI total scores (p = 0.002), and no differences were found in BFI total score after exposure to neoadjuvant chemotherapy (p = 0.92). In a linear regression model, only exposure to RT (β = - 5.1; 95% CI - 8.9 to - 1.3; p = 0.008) and tumor distance from the anal verge (β = 1.23; 95% CI 0.48 to 1.97; p = 0.001) were significantly correlated with BFI total score.Conclusion: NC, whether administered alone or added to CRT, does not seem to impair bowel function. These data should be used to counsel rectal cancer patients when discussing neoadjuvant therapy options. [ABSTRACT FROM AUTHOR]

Myeloid translocation genes (MTGs) are transcriptional corepressors originally identified in acute myelogenous leukemia that have recently been linked to epithelial malignancy with non-synonymous mutations identified in both MTG8 and MTG16 in colon, breast, and lung carcinoma in addition to functioning as negative regulators of WNT and Notch signaling. A yeast two-hybrid approach was used to discover novel MTG binding partners. This screen identified the Zinc fingers, C2H2 and BTB domain containing (ZBTB) family members ZBTB4 and ZBTB38 as MTG16 interacting proteins. ZBTB4 is downregulated in breast cancer and modulates p53 responses. Because ZBTB33 (Kaiso), like MTG16, modulates Wnt signaling at the level of TCF4, and its deletion suppresses intestinal tumorigenesis in the ApcMin mouse, we determined that Kaiso also interacted with MTG16 to modulate transcription. The zinc finger domains of Kaiso as well as ZBTB4 and ZBTB38 bound MTG16 and the association with Kaiso was confirmed using co-immunoprecipitation. MTG family members were required to efficiently repress both a heterologous reporter construct containing Kaiso binding sites (46KBS) and the known Kaiso target, Matrix metalloproteinase-7 (MMP-7/Matrilysin). Moreover, chromatin immunoprecipitation studies placed MTG16 in a complex occupying the Kaiso binding site on the MMP-7 promoter. The presence of MTG16 in this complex, and its contributions to transcriptional repression both required Kaiso binding to its binding site on DNA, establishing MTG16- Kaiso binding as functionally relevant in Kaiso-dependent transcriptional repression. Examination of a large multi-stage CRC expression array dataset revealed patterns of Kaiso, MTG16, and MMP-7 expression supporting the hypothesis that loss of either Kaiso or MTG16 can de-regulate a target promoter such as that of MMP-7. These findings provide new insights into the mechanisms of transcriptional control by ZBTB family members and broaden the scope of co-repressor functions for the MTG family, suggesting coordinate regulation of transcription by Kaiso/MTG complexes in cancer. [ABSTRACT FROM AUTHOR]