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Objective: The purpose of this study was to investigate the effect of a single dose of ethanol on rat adrenal cortex and to determine whether the estrous cycle can influence this effect of ethanol. Method: Adult female Wistar rats showing proestrus or diestrus Day 1 (n = 121 were treated intraperitoneally with ethanol (4 g/kg body weight). Untreated (n = 15) and saline-injected (n = 14) rats were used as controls. The animals were sacrificed by decapitation 0.5 hour after ethanol administration. Stereological analysis was performed on paraffin sections of adrenal glands stained with AZAN, and the following parameters were determined: absolute volume of the zona glomerulosa, the zona fasciculata and the zona reticularis, numerical density, volume and the mean diameter of adrenocortical cells and of their nuclei, and diameter and length of capillaries. Results: The diameter and volume of adrenocortical cells in the zona fasciculata and the zona reticularis were significantly increased by acute ethanol treatment at proestrus. In the same group of animals, a single dose of ethanol induced significant decrease in numerical density of adrenocortical cells and of their nuclei in all three zones. Increased length of capillaries of the zona fasciculata as well as enhanced level of serum corticosterone was found in ethanol-treated rats at both phases of the estrous cycle, proestrus and diestrus Day 1. Conclusions: The obtained results indicate that a single dose of ethanol activates adrenal cortex in female rats and that the effect is more pronounced on morphometric parameters at proestrus., ACTIVATION OF the hypothalamic-pituitary-adrenal (HPA) axis is a central component of the adaptive response to preserve neuroendocrine homeostasis. Ethanol is known to stimulate the HPA axis of both experimental animals [...]

Constitutive activation of the Wnt signaling pathway is a root cause of many colon cancers. Activation of this pathway is caused by genetic mutations that stabilize the β-catenin protein, allowing it to accumulate in the nucleus and form complexes with any member of the lymphoid enhancer factor (LEF1) and T-cell factor (TCF1, TCF3, TCF4) family of transcription factors (referred to collectively as LEF/TCFs) to activate transcription of target genes. Target genes such as MYC, CCND1, MMP7 and TCF7 (refs. 5-9) are normally expressed in colon tissue, so it has been proposed that abnormal expression levels or patterns imposed by β-catenin/TCF complexes have a role in tumor progression. We report here that LEF1 is a new type of target gene ectopically activated in colon cancer. The pattern of this ectopic expression is unusual because it derives from selective activation of a promoter for a full-length LEF1 isoform that binds β-catenin, but not a second, intronic promoter that drives expression of a dominant-negative isoform. β-catenin/TCF complexes can activate the promoter for full-length LEF1, indicating that in cancer high levels of these complexes misregulate transcription to favor a positive feedback loop for Wnt signaling by inducing selective expression of full-length, β-catenin-sensitive forms of LEF/TCFs. [ABSTRACT FROM AUTHOR]

Abstract: Background: Levamisole (LMS) has immunomodulatory activity, stimulates the immune system of healthy, normal volunteers and has been proposed previously as a colon cancer preventive agent. Methods: Patients with a history of colonic polyps who are at increased risk of colon cancer received LMS in a placebo-controlled, double-blinded clinical trail with crossover design. Primary endpoints were immunologic and included flow cytometry of peripheral blood mononuclear cells (PBMCs), measurement of interferon-γ copy number (IGCN) in PBMCs, and an ex vivo serum immune assay. Results: No differences were seen in the expression of multiple antigens by flow cytometry pre- and post-LMS. The IGCN partitioned subjects into two distinct groups defined by a γ-distribution which had a differential response to LMS. Those with low basal IGCN had a lower percentage of CD25 expressing PBMCs and responded to low dose LMS by producing more PBMC-derived interferon-γ and increasing the expression of CD25 and two NK cell markers, CD16 and CD56. In contrast, subjects with a high basal IGCN responded to low dose LMS with a reduction in PBMC-derived interferon-γ and a decrease in the expression of CD25. Conclusions: In aggregate, these responses suggest that LMS may act as an immunostimulatory agent for one group, those with low basal IGCN, and as an immunosuppressive agent for the other. LMS may not be an optimal agent for most patients with colonic polyps and should be avoided in patients with normal immune function. IGCN may be useful as an immunologic surrogate endpoint biomarker in future cancer prevention trials with immunomodulatory agents. [Copyright &y& Elsevier]

We have evaluated the expression of Kit, a receptor encoded by the c-kit protooncogene, and platelet-derived growth factor-receptors (PDGF-R) alpha and beta in cholangiocarcinoma specimens from 13 separate patients, and provide a case report of a therapeutic trial of imatinib mesylate in one patient. Archived pathologic samples from 13 patients with cholangiocarcinoma were obtained. Tissue sections were hybridized with anti-Kit, anti-PDGF-Ralpha and anti-PDGF-Rbeta monoclonal antibodies. Kit, PDGF-Ralpha and PDGF-Rbeta expression was seen in 31, 69 and 46% of samples, respectively. All patients with PDGF-Rbeta expression also expressed PDGF-Ralpha. Three out of four patients with Kit expression did not express either PDGF receptor and only one patient exhibiting expression of PDGF expressed Kit. Cohen's kappa statistic demonstrated that PDGF and Kit expression were inversely correlated with borderline significance (p=0.052; kappa=-0.4742, 95% confidence interval -0.9821 to 0.03364). In one case, strong Kit expression was noted in a tumor from a metastatic lymph node, but was absent in the primary tumor, suggesting that Kit may be related to invasive or metastatic potential. Given the high level of expression defined in this study, a prospective clinical trial incorporating imatinib mesylate, alone or in combination with cytotoxic chemotherapy, and especially in chemotherapy-naive patients, should be considered for patients with cholangiocarcinoma.