The wheel-running activity rhythm of tree shrews (tupaias; Tupaia belangeri) housed in constant darkness (DD) phase-advanced following a 3-hr light pulse at circadian time (CT) 21. Dark pulses of 3 hr presented to tupaias in bright constant light (LL) did not induce significant phase shifts of the free-running activity rhythm, irrespective of the CT. In dim LL, tupaias showed simultaneous splitting of their circadian rhythm of wheel-running activity, nest-box activity, and feeding behavior. Light pulses of 6 hr and 2300 lux were presented to 13 tupaias with split wheel-running activity rhythms. These light pulses induced immediate phase shifts in the two components of the split rhythm in opposite directions. No differences were observed between the light-pulse phase response curves of the two components. Equally large immediate phase advances were induced in both components by light pulses of 230 lux, but not by 23 lux. The final phase shifts were small at all CTs. In two tupaias, activity rhythms transiently split and re-fused. Analysis of the relative position of the components in one of these indicates asymmetry in the coupling between the components.
BackgroundColorectal cancer is a preventable disease if caught at early stages. This disease is highly aggressive and has a higher incidence in African Americans. Several biomarkers and mutations of aggressive tumor behavior have been defined such as metastasis-associated in colon cancer 1 (MACC1) that was associated with metastasis in colorectal cancer patients. Here, we aim to assess colon tissue MACC1 protein and circulating MACC1 transcripts in colon preneoplastic and neoplastic African American patients.MethodsPatients’ tissue samples (n = 143) have been arranged on three tissue microarrays for normal (n = 26), adenoma (n = 68) and cancer (n = 49) samples. Immunohistochemistry was used to detect MACC1 expression. Blood samples (n = 93) from normal (n = 45), hyperplastic (n = 15) and tubular adenoma (n = 33) patients were used to assess MACC1 transcripts using qRT-PCR. Distribution of continuous variables was tested between different diagnoses with Kruskal–Wallis test. Categorical variables were tested by Chi square test. We assessed the prognostic ability of IHC staining by calculating area under receiver operating characteristics curve (ROC) for adenoma and cancer separately. Differences between groups in terms of MACC1 transcript levels in plasma were calculated by using non-parametric (exact) Wilcoxon-Mann–Whitney tests. We performed all calculations with SPSS, version 21.ResultsIn patient tissues, there was a statistically significant difference in MACC1 expression in normal vs. adenoma samples (p = 0.004) and normal vs. cancer samples (p < 0.001). There was however no major difference in MACC1 expression between adenoma vs. cancer cases or tubular adenomas vs tubulovillous adenomas. The area under the curve for both normal vs. adenoma and normal vs. cancer cases were 70 and 67 %, respectively. MACC1 expression was not correlated to age, gender or anatomical sample location. In patient plasma, MACC1 transcripts in adenoma patients were significantly higher than in plasma from normal patients (p = 0.014). However, the difference between normal and hyperplastic plasma MACC1 transcripts was not statistically significant.ConclusionMetastasis-associated in colon cancer 1 is expressed at early stages of colorectal oncogenesis within the affected colonic tissue in this patient cohort. The plasma transcripts can be used to stratify African American patients at risk for potential malignant colonic lesions.
Background: Several studies have reported the detection of Metastatic Associated Colon Cancer 1 (MACC1) in colorectal cancer (CRC) patients’ tissues and blood. However the expression of this marker in earlier stages has not been investigated. Aim: To determine MACC1 expression in colonic adenoma, CRC, and blood of African Americans (AA). Materials & Methods: Three tissue microarrays of normal (n=32), adenoma (n=74) and CRC (n=46) tissues from AA patients were constructed. Immunohistochemistry (IHC) using an anti-MACC1 antibody was performed. The stained slides were read by two pathologists who were blinded as to the samples diagnosis. Both staining intensity and percentage were established. The IHC results were analyzed in light of the demographic and pathological characteristics of the patients. Plasma samples from normal (n=45), hyperplastic (HPP; n=15) and tubular adenoma (n=33) patients were tested for MACC1 transcripts. A Mann Whitney Rank Sum Test was used to assess the statistical differences in MACC1 transcripts’ detection. Results: The TMA staining revealed MACC1 expression in all three TMAs including the normals. These normals correspond to adjacent tissues to cancer samples which might explain the MACC1 staining. Male gender showed an increase of MACC1 expression in all three TMA separately or combined (p<0.05). The diagnostic ability of MACC1 was good in the adenoma samples when compared to the normal with an AUC=0.65 (95%CI: 0.55-0.74). The cytoplasmic staining percentage in adenomas had the best combination of sensitivity (0.77) and specificity (0.56). This diagnostic value was less significant in cancer samples (AUC=0.51 (95%CI: 0.43-0.58)). MACC1 transcripts were significantly more expressed in colonic lesions samples when compared to normal patients’ plasma (normal vs. (TA+HPP), p=0.014; normal vs. TA: p=0.011). However, MACC1 transcription in normal vs. HPP samples, was not statically significant (P=0.239). Conclusion: Here we demonstrate that MACC1 is expressed very early in the carcinogenic process since it was detected in adenoma tissue from AA. Its correlation with male gender cannot be explained at this time as there are no epidemiological data that support gender associated metastatic phenotype. MACC1 plasma transcripts reveal that this marker is not only detectable in preneoplastic lesions but also released in patients’ circulation. This finding might be capitalized on to determine colonic lesions with potential metastatic characteristics. [U.S. and H.A. contributed equally to this work.] Citation Format: Hassan Brim, Pia Hermann, Mehdi Nouraie, Babak Shokrani, Ed Lee, Tahmineh Haidary, Hassan Ashktorab, Ulrik Stein. Can MACC1 plasma transcripts in colon adenoma patients be used as an early indicator of metastasis potential. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 553. doi:10.1158/1538-7445.AM2014-553
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