A rare case of signet ring cell carcinoma with diffuse cutaneous systemic sclerosis: A case report.

Systemic sclerosis, an autoimmune disease characterized by fibrosis and vasculopathy of the skin and other multiple organs has been associated with an increased risk of malignancy. We present the case of a 74-year-old woman who had diffused cutaneous systemic sclerosis and uterine cervical cancer. The patient was initially diagnosed with stage IIB squamous cell carcinoma and concurrent chemoradiotherapy was planned. However, cisplatin could not be administered due to acute renal failure, so the patient was treated solely with radiotherapy. However, complications of systemic sclerosis progressed rapidly, and the patient died 63 days later from pulmonary edema. An autopsy later revealed that uterine cervix had primary signet ring cell carcinoma. We suspected that this patient had a combination of signet ring cell carcinoma and squamous cell carcinoma, with squamous cell carcinoma disappearing after radiotherapy. This case highlighted the importance of systemic management for cancers associated with systemic sclerosis.

Neutral endopeptidase expressed by decidualized stromal cells suppresses akt phosphorylation and deoxyribonucleic acid synthesis induced by endothelin-1 in human endometrium.

Endothelin-1 (ET-1) in human endometrium has been proposed to have a potential paracrine role, for its receptors are also present within this tissue. In addition, the expression of ET-1 varies during the menstrual cycle, and therefore, ET-1 may be involved in the cyclic change of the human endometrium, such as proliferation and decidualization. However, neither the inactivation of ET-1 in the endometrium nor the paracrine effect of ET-1 on endometrial cells has been determined. We investigated the production of ET-1 and the presence of neutral endopeptidase (NEP), which cleaves and inactivates ET-1, in primary cultured human endometrial cells. We found primary cultured endometrial epithelial cells, not stromal cells, to be the major source of ET-1. Western blot analysis and RT-PCR demonstrated that NEP was predominantly expressed by endometrial stromal cells. We also demonstrated that ET-1 stimulated the phosphorylation of Akt and DNA synthesis in endometrial stromal cells via the ET(A) receptor and phospahtidylinositol-3 kinase signaling pathways. The effect of ET-1 was regulated by NEP expressed by stromal cells. We also found that conditioned medium containing ET-1 from endometrial epithelial cell culture stimulated phosphorylation of Akt via the ET(A) receptor. In conclusion, ET-1 has a paracrine effect of Akt phosphorylation and cell proliferation on endometrial stromal cells, which occurs via the ET(A) receptor and phospahtidylinositol-3 kinase signaling pathways, and is regulated by cell-surface NEP.

Distribution of adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase (ERAP)-1 in human uterine endometrium.

Adipocyte-derived leucine aminopeptidase (A-LAP, endoplasmic reticulum aminopeptidase ERAP1) is specialized to produce peptides presented on the class I major histocompatibility complex (MHC) by trimming epitopes to eight or nine residues, in addition to its enzymatic activity to degrade angiotensin II. Previously we identified placental leucine aminopeptidase (P-LAP), another member of the oxytocinase subfamily of aminopeptidases, in human uterine endometrial epithelial cells. Here we analyzed the distribution of A-LAP in human cyclic endometrium. Western blotting analysis showed that A-LAP was present in the endometrial tissue throughout the menstrual cycle. Immunohistochemical (IHC) analysis of A-LAP showed a similar distribution to that of P-LAP. A-LAP was localized predominantly in the endometrial glands and the luminal surface epithelium. However, the intracellular localization change that accompanied apocrine secretion, which was observed in P-LAP, was not shown in A-LAP. Subcellular localization of A-LAP, demonstrated by immunofluorescence, was ER in the cultured glandular epithelial cells. Our results indicate that A-LAP may fit the endometrial localization as an antigen-presenting ER aminopeptidase. Further understanding of the function(s) of A-LAP in the endometrium appear likely to yield insights into the cyclic changes during the normal endometrial cycle.

Dual renin-angiotensin blockade therapy in patients at high risk of early ovarian hyperstimulation syndrome receiving IVF and elective embryo cryopreservation: a case series.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an important and dangerous aspect of assisted reproduction techniques. Although elective cryopreservation of all embryos can prevent pregnancy-induced late OHSS, it cannot prevent early OHSS, which is induced by hCG administration. METHODS: We undertook this trial to assess the efficacy with which the combined oral administration of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) could prevent early OHSS in IVF patients at very high risk for this syndrome. Four women, who had serum estradiol concentration > or =8000 pg/ml on the day of hCG injection, were treated with the combination of the ACEI alacepril and the ARB candesartan cilexetil for 8 days starting the day after oocyte retrieval. Embryos were cryopreserved and embryo transfer was postponed until later cycles. RESULTS: Despite the extremely enlarged ovaries, no ascites was accumulated in any of the cases. Haematocrit (34.1 +/- 1.0) and serum albumin concentration (4.1 +/- 0.2 g/dl) were normal throughout the treatment period. These patients showed elevated plasma renin and angiotensin II concentration before the treatment. CONCLUSIONS: The dual renin-angiotensin blockade therapy used here would be worth exploring further in a study with more patients and a prospective, randomized design.