Transmural eosinophilic gastritis with gastric outlet obstruction: case report and review of the literature.

Eosinophil-associated gastrointestinal disorders (EGIDs) are uncommon conditions whose aetiologies are unclear, but which are characterised by eosinophilic infiltration and inflammation of the gastrointestinal tract in the absence of other causes of eosinophilia. We report the case of a 65-year-old woman with eosinophilic gastritis who underwent a Polya gastrectomy for a suspected gastric tumour with gastric outflow obstruction. Subsequent histological examination showed a non-malignant transmural eosinophilic infiltration of the stomach wall, a rare pathological entity. We present a review of the literature and discuss the management of such cases.

Differential effects of toremifene on doxorubicin, vinblastine and Tc-99m-sestamibi in P-glycoprotein-expressing breast and head and neck cancer cell lines.

The effect of toremifene on P-glycoprotein-mediated multidrug resistance (MDR) in breast and head and neck cancer cell lines was measured in vitro and in vivo. Pgp expression was low and high, respectively, in drug-sensitive (MCF7-S, KB) and drug-resistant (MCF7-R, MCF7-R1, KBV1) cell lines. Toremifene (7.5 microM) significantly enhanced cytoplasmic and nuclear accumulation of doxorubicin in drug-resistant cells. Toremifene (10 microM) increased the in vitro cytotoxicity of doxorubicin in drug-resistant breast cancer cells (13-fold and 21-fold for MCF7-R and MCF7-R1, respectively) without affecting the sensitivity of MCF7-S cells. Similarly, toremifene (10 microM) caused a 12-fold increase in the sensitivity of KBV1 cells to vinblastine. In contrast, toremifene (5 microM) reduced the net uptake of the radiolabelled Pgp substrate, Tc-99m-sestamibi, in the Pgp-overexpressing cell lines by factors of 0.32 and 0.42 for MCF7-R1 and KBV1 cells, respectively (p < 0.01), and, to a lesser extent, by corresponding factors of 0.89 and 0.86 in the drug-sensitive cell lines (p < 0.05 and p > 0.05, respectively). In nude mice bearing both KB and KBV1 xenograft tumours, significantly higher tumour levels of Tc-99m-sestamibi were recorded in KB tumours compared with KBV1 tumours. After 3 days of treatment with intraperitoneal toremifene (25 mg/kg), tumour levels of Tc-99m-sestamibi were reduced in KB and KBV1 tumours but only statistically significantly for KB tumours. Toremifene is a potent MDR modulating agent with respect to chemotherapeutic agents but has the opposite effect with respect to Tc-99m-sestamibi. This finding is of importance in view of the widespread use of Tc-99m-sestamibi as an imaging surrogate for a chemotherapeutic agent.

Ligand activation of the androgen receptor downregulates E-cadherin-mediated cell adhesion and promotes apoptosis of prostatic cancer cells.

Androgen independence is the major cause of endocrine therapy failure in advanced prostate cancer (PC). To examine the effects of human androgen receptor (AR) expression on growth of human PC cells, transfection of full-length AR cDNA in an androgen-insensitive human prostatic adenocarcinoma cell line (DU145) was performed. Transcriptional activity of AR was confirmed by the MMTV luciferase assay and AR expression was assessed by reverse transcriptase polymerase chain reaction, Western blotting, and immunocytochemistry. Two stable transfectant cell lines expressing functional AR were established and passaged over 60 times. Under standard culture conditions, AR expression in transfected cells was predominantly cytoplasmic. Exposure to dihydrotestosterone (DHT; 60 pM-10 nM) resulted in a rapid (maximal at 30 minutes) translocation of AR to the nucleus. Treatment with DHT (5 nM) caused a significant reduction in cell-cell adhesion and aggregation accompanied by a decrease in E-cadherin expression. This was associated with up to 40% inhibition of proliferation and approximately two-fold increase in apoptosis. These results suggest that gene transfer-mediated AR expression in DU145 cells confers sensitivity to DHT, modulates cell-cell adhesion through E-cadherin, and suppresses cell growth by inhibiting proliferation and promoting apoptosis. This provides amodelfor studies ofAR-regulated cell signalling and identification of novel androgen-regulated genes in PC.

99mTc-sestamibi imaging in the assessment of toremifene as a modulator of multidrug resistance in patients with breast cancer.

UNLABELLED: Multidrug resistance (MDR) due to expression of a membrane-associated permeability glycoprotein (P-glycoprotein [Pgp]) prevents successful cytotoxic chemotherapy for breast cancer. Identification of MDR would facilitate selection of chemotherapy regimens and MDR modulators. This study aimed to evaluate (99m)Tc-sestamibi imaging for predicting overexpression of Pgp in primary breast cancer and to measure the efficacy of toremifene, the MDR modulator, in vivo. METHODS: Twenty patients with untreated breast cancer had (99m)Tc-sestamibi imaging 20 and 120 min after tracer injection before and after a 3-d course of toremifene (780 mg/d). Tumor samples were obtained during surgery for correlation of imaging and Pgp immunohistochemistry. RESULTS: Sixteen of 20 tumors were visualized with sestamibi. Before toremifene, there was a significant inverse correlation (Spearman rank correlation coefficient [R(S)]) between staining intensity, based on the anti-Pgp monoclonal antibodies C494 and C219, and the tumor-to-background ratio (T/B) at 120 min (R(S) = -0.85; P < 0.001 and R(S) = -0.71; P < 0.001, respectively). However, the correlation between the T/B and immunohistochemistry at 20 min was significant only for C494 (R(S) = -0.57; P < 0.01). Similarly, before toremifene, there was an inverse correlation between staining intensity and the change in the T/B between 20 and 120 min (R(S) = -0.77; P < 0.001 and -0.75; P < 0.001 for C494 and C219). After toremifene, an inverse correlation between staining intensity and the T/B was seen only at 120 min and only with C494 (R(S) = -0.68; P < 0.01). However, the change in the T/B between 20 and 120 min correlated significantly with staining intensity for C494 and C219 (R(S) = -0.68; P < 0.01 and -0.7; P < 0.01 for C494 and C219, respectively). Toremifene did not significantly alter the overall T/B at either 20 or 120 min when data were compared before and after toremifene. Nevertheless, at 120 min, 8 of 8 tumors with low Pgp expression showed reduced uptake after toremifene, whereas 5 of 6 tumors with strong expression showed increased uptake (P < 0.003). Moreover, there was a significant correlation between the change in the T/B and staining intensity with C494 (R(S) = 0.59; P < 0.05) and C219 (R(S) = 0.56; P < 0.05) at 120 min but not at 20 min. CONCLUSION: (99m)Tc-Sestamibi accumulation in breast cancer correlates with Pgp expression. Toremifene has a dual effect on this accumulation, increasing it through an inhibitory effect on Pgp while at the same time reducing it by a direct competition with sestamibi. The latter implies that in response to Pgp modulation the efflux of various agents may be affected differently.

MUC1 mucin and trefoil factor 1 protein expression in renal cell carcinoma: correlation with prognosis.

This study examines the coexpression of MUC1 mucin and trefoil factor 1 (TFF1) and their relationship to progression of renal cell carcinoma (RCC). Immunohistochemistry was performed on tumor and adjacent normal tissue from clear-cell RCC (n = 60) and tissues from normal controls (n = 5) using a set of well-characterized monoclonal antibodies recognizing different epitopes of MUC1 and TFF1. Results of immunohistochemistry were compared with clinical parameters, including tumor grade, tumor size, presence of metastasis, and progression-free survival of patients after surgery. In normal tissue, MUC1 and TFF1 were absent from the normal proximal tubular epithelium but were identified in distal and collecting tubular epithelium. In RCC, increased MUC1 expression positively correlated to tumor progression. MUC1 recognized by HMFG1 was associated with large tumor size (P < .05), distant metastasis (P < .05), and invasion of large veins (P < .05). Expression of the under-glycosylated form of MUC1 recognized by SM3 was found to correlate to time to progression (recurrence, metastasis, or death of patient; P < .001). Expression of TFF1 did not significantly correlate with any prognostic parameters. However, there was a significant correlation (P < .01) between TFF1 and MUC1 expression (HMFG2 epitope) in RCCs. These results are consistent with the following conclusions: (1) MUC1 may be an independent prognostic marker in RCC; (2) TFF1 is frequently coexpressed with MUC1 and may act synergistically; and (3) RCC may originate from distal tubular epithelium.