Sertoli-Leydig cell tumor with unique nail findings in a post-menopausal woman: a case report and literature review.

BACKGROUND: Sertoli-Leydig cell tumor (SLCT) is a rare sex-cord tumor that usually occurs unilaterally and accounts for < 0.5% of all ovarian tumors. SLCT is uncommon in post-menopausal women, with the average age of diagnosis being 25 years. CASE: We present a case of a 63-year-old post-menopausal woman presenting with progressive hirsutism, and male-pattern baldness. Unusual nail changes were also observed. METHODS: Hormonal profile of the patient revealed increased testosterone and estradiol levels, and a 3.5 cm left ovarian mass. The patient was evaluated and was not found to be anemic or iron-deficient. Intraoperative frozen section assessment during laparoscopic exploration revealed SLCT, which was confirmed subsequently by histopathological and immunohistochemical (IHC) examination. Nail bed tissues were collected from normal females and evaluated by IHC for the presence of androgen receptors (AR). RESULTS: The patient had an excellent postoperative course and all her testosterone-related manifestations were reversed within one year of surgery. Following surgery, the patient's unique nail abnormalities also resolved gradually. The IHC evaluation also confirmed the presence of AR in nail bed tissues of females. CONCLUSION: SLCT, albeit rare, should be considered in post-menopausal women presenting with virilization and elevated androgen levels. Unusual nail signs may develop in response to increased androgen levels in these patients.

Green tea extract inhibition of human leiomyoma cell proliferation is mediated via catechol-O-methyltransferase.

BACKGROUND/AIMS: To investigate the inhibitory effect of green tea extract, epigallocatechin gallate (EGCG), on wild-type human leiomyoma (WT-HuLM) cells and its potential action via catechol-o-methyltransferase (COMT) activity. METHODS: Cell proliferation of WT-HuLM and COMT gene-silenced HuLM (COMT-shRNA-HuLM) cells treated with 0 or 100 µM EGCG for 7 days was measured using the MTT method. Total RNA and protein were extracted from cells treated with 0 or 100 µM of EGCG for 48 h. Gene expression profiling was performed using Human Signal Transduction PathwayFinder. Proliferation cell nuclear antigen (PCNA), cyclin-dependent kinase 4 (Cdk4) and COMT protein levels were detected by Western blot analyses. COMT enzyme activity was evaluated by HPLC. RESULTS: EGCG-treated WT-HuLM cells showed significantly decreased COMT expression (p < 0.001) and enzyme activity (p < 0.05) compared to untreated WT-HuLM cells, while COMT-shRNA-HuLM cells showed no significant change. At 100 µM of EGCG, survival of WT-HuLM cells was significantly lower (p < 0.05) compared to COMT-shRNA-HuLM cells. EGCG treatment modulated multiple signaling pathways in WT-HuLM compared to untreated control, while changes were minimal or reversed in COMT-shRNA-HuLM cells. EGCG significantly decreased PCNA, Cdk4 and soluble COMT protein levels (p < 0.001) in WT-HuLM, but not in COMT-shRNA-HuLM cells. CONCLUSIONS: The antiproliferative and gene-modulating effects of EGCG on HuLM cells are mediated, at least partially, via its effect on COMT expression and enzyme activity.

Paricalcitol, a vitamin d receptor activator, inhibits tumor formation in a murine model of uterine fibroids.

We examined the antitumor and therapeutic potentials of paricalcitol, an analog of 1,25-dihydroxyvitamin D3 with lower calcemic activity, against uterine fibroids using in vitro and in vivo evaluations in appropriate uterine fibroid cells and animal models. We found that paricalcitol has potential to reduce the proliferation of the immortalized human uterine fibroid cells. For the in vivo study, we generated subcutaneous tumors by injecting the Eker rat-derived uterine leiomyoma cell line (ELT-3) rat uterine fibroid-derived cell line in athymic nude mice supplemented with estrogen pellets. These mice were administered with vehicle versus paricalcitol (300 ng/kg/d) or 1,25-dihydroxyvitamin D3 (500 ng/kg/d) for 4 consecutive weeks, and the data were analyzed. We found that while both paricalcitol and 1,25-dihydroxyvitamin D3 significantly reduced fibroid tumor size, the shrinkage was slightly higher in the paricalcitol-treated group. Together, our results suggest that paricalcitol may be a potential candidate for effective, safe, and noninvasive medical treatment option for uterine fibroids.

Krukenberg tumor presenting as back pain and a positive urine pregnancy test: a case report and literature review.

A Krukenberg tumor is a rare and potentially deadly cause of elevated serum ß-hCG as part of a paraneoplastic syndrome. This study aims to describe the unusual case of a 36-year-old woman that presented to the Emergency Department (ED) with back pain and a positive urine pregnancy test. Assessment revealed no intrauterine pregnancy and a small left ovarian cyst. Further investigation showed moderately differentiated gastric adenocarcinoma with distant metastases to the spine. The patient died less than 3 months after her first presentation to the ED. Paraneoplastic syndrome, albeit rare, should be considered in the differential diagnosis of elevated ß-hCG due to the high mortality associated with Krukenberg tumors.

TLR2 and Nod2 mediate resistance or susceptibility to fatal intracellular Ehrlichia infection in murine models of ehrlichiosis.

Our murine models of human monocytic ehrlichiosis (HME) have shown that severe and fatal ehrlichiosis is due to generation of pathogenic T cell responses causing immunopathology and multi-organ failure. However, the early events in the liver, the main site of infection, are not well understood. In this study, we examined the liver transcriptome during the course of lethal and nonlethal infections caused by Ixodes ovatus Ehrlichia and Ehrlichia muris, respectively. On day 3 post-infection (p.i.), although most host genes were down regulated in the two groups of infected mice compared to naïve counterparts, lethal infection induced significantly higher expression of caspase 1, caspase 4, nucleotide binding oligomerization domain-containing proteins (Nod1), tumor necrosis factor-alpha, interleukin 10, and CCL7 compared to nonlethal infection. On day 7 p.i., lethal infection induced highly significant upregulation of type-1 interferon, several inflammatory cytokines and chemokines, which was associated with increased expression levels of Toll-like receptor-2 (TLR2), Nod2, MyD88, nuclear factor-kappa B (NF-kB), Caspase 4, NLRP1, NLRP12, Pycard, and IL-1ß, suggesting enhanced TLR signals and inflammasomes activation. We next evaluated the participation of TLR2 and Nod2 in the host response during lethal Ehrlichia infection. Although lack of TLR2 impaired bacterial elimination and increased tissue necrosis, Nod2 deficiency attenuated pathology and enhanced bacterial clearance, which correlated with increased interferon-γ and interleukin-10 levels and a decreased frequency of pathogenic CD8(+) T cells in response to lethal infection. Thus, these data indicate that Nod2, but not TLR2, contributes to susceptibility to severe Ehrlichia-induced shock. Together, our studies provide, for the first time, insight into the diversity of host factors and novel molecular pathogenic mechanisms that may contribute to severe HME.