Ilan Aroch

Curcumin potentiates the pro-apoptotic effects of sulindac sulfone in colorectal cancer

Objective: The use of sulindac sulfone (SFN) for colorectal cancer (CRC) therapy is limited due to its toxicity. The present study was carried out to examine whether curcumin, a novel chemopreventive agent, can potentiate the effects of low dosages of SFN in CRC treatment. Methods: HT-29 CRC cells were exposed to SFN (200 – 400 microM), curcumin (5 – 10 microM) or their combination. The cytotoxic effects of the drugs were evaluated using growth inhibition assays. Annexin V/PI and cell cycle analysis were employed to study the mechanism of action of the drugs. The therapeutic efficacy of the drugs in vivo was examined using the aberrant crypt foci (ACF) model. The treatment groups included eight rats/group. Results: Treatment of cells with curcumin and SFN resulted in a synergistic inhibitory effect of 50 – 90% (p < 0.005) on cell growth. Growth inhibition was associated with inhibition of proliferation, G2/M arrest and induction of apoptosis. Administration of curcumin (0.6%) and SFN (0.06%) to 1, 2-dimethylhydrazine treated rats significantly reduced (by 75%, p < 0.01) the number of ACF. Conclusions: Curcumin augments the therapeutic effects of SFN. This may be clinically important since the addition of curcumin to low dosages of SFN may encourage a safer and potent combinatorial treatment regimen for CRC.

ORIGINAL ARTICLE: Effect of Maternal Immunopotentiation on Apoptosis‐Associated Molecules Expression in Teratogen‐Treated Embryos

Problem  Potentiation of the maternal immune system was shown by us to affect the embryonic response to teratogenic insults. In order to understand better the mechanisms underlying that phenomenon, we explored the effect of maternal immunopotentiation by rat splenocytes on the early stages of the embryonic response to cyclophosphamide (CP).

ORIGINAL ARTICLE: Effect of Maternal Immunopotentiation on Apoptosis-Associated Molecules Expression in Teratogen-Treated Embryos: IMMUNOPOTENTIATION-MEDIATED EMBRYONIC RESPONSE TO CP

Problem  Potentiation of the maternal immune system was shown by us to affect the embryonic response to teratogenic insults. In order to understand better the mechanisms underlying that phenomenon, we explored the effect of maternal immunopotentiation by rat splenocytes on the early stages of the embryonic response to cyclophosphamide (CP).

Effect of maternal immunopotentiation on apoptosis-associated molecules expression in teratogen-treated embryos.

Problem  Potentiation of the maternal immune system was shown by us to affect the embryonic response to teratogenic insults. In order to understand better the mechanisms underlying that phenomenon, we explored the effect of maternal immunopotentiation by rat splenocytes on the early stages of the embryonic response to cyclophosphamide (CP).

Abstract 2902: A simple blood test, evaluating the level of CD24 protein, can detect subjects with colorectal adenomas and adenocarcinomas

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: CD24 is a cell surface protein involved in cell adhesion and metastasis. Using gene expression array we have shown that CD24 expression is associated with colorectal cancer (CRC) [1,2]. The data was confirmed by IHC staining showing expression of CD24 in ∼90% of CR adenomas and adenocarcinomas. Two genetic variants of CD24, a C to T single nucleotide polymorphism (SNP), leading to an Ala/Val exchange (A57V) and a TG deletion in the 3’-UTR have been described, may have functional relevance, and affect CD24 protein level and stability. Objectives: To evaluate CD24 protein expression in peripheral blood leukocytes (PBLs) from normal, adenoma and CRC subjects, and score the associations of CD24 genetic variants and CRC risk. Methods: The calibration trial included 150 consented subjects (CRC=63, Adenomas=19, Normal=68) attending Tel Aviv Medical Center that underwent colonoscopy. PBLs were isolated and analyzed by Western blotting using anti-CD24. The samples were externally evaluated at the Technion, Haifa. The validation trial included 73 subjects. Additional 83 subjects were recently examined. Band intensities were scanned and tested for statistical significance. Sensitivity and specificity for CD24 was determined using receiver operating characteristic (ROC) curves. The study was approved by the Israel Ministry of Health. Results: The sensitivity and specificity of the CD24 test for distinguishing CRC from normal subjects was 70.5% (95% CI, 54.8-83.2%) and 83.8% (95% CI, 74.6-92.7%), respectively, and for advanced adenomas 84.2% (95% CI, 60.4-96.4%) and 73.5% (95% CI, 61.4-83.5%), respectively. The external evaluation study varied slightly. Improved values were achieved in the validation trial. Thus, the sensitivity for the detection of CRC was 92.3% (95% CI, 63.9-98.7%), with similar specificity, whereas the specificity for detecting adenomas was higher, 89.2% (95% CI, 74.6-96.9%). No significant correlations were found between the expression of CD24 and the two SNPs examined. However, preliminary data shows that the P170 C/T variant may increase susceptibility to CR adenomas (p=0.048) while the TG/del CD24 SNP may have a protective role (NS). Conclusions: The CD24 blood test is the first of its kind to be able to detect adenomas. It can also successfully distinguish CRC from healthy subjects. CD24 may serve as a potential and promising biomarker for the early detection of CRC. Larger studies are warranted to establish the future potential of this promising test. References: 1. Sagiv E., Gastroenterology 2006 2. Sagiv E., Can Res, 2008 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2902.