Raf-1, a potential therapeutic target, mediates early steps in endometriosis lesion development by endometrial epithelial and stromal cells

Endometriosis is a hormone-sensitive gynecological disorder characterized by the benign growth of endometrial-like tissue in the pelvic cavity. Endometriotic lesions composed of endometrial stromal cells (ESC) and glandular epithelial cells (EEC) are thought to arise from menstrual endometrial tissue reaching the pelvic cavity via retrograde menstruation. The cause of endometriotic lesion formation is still not clear. Recent evidence suggest that cytokines may play a role in the early development of endometriosis lesions. Because cytokines and growth factors signal via the v-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) kinase pathway, we have examined the role of Raf-1 in early steps of endometriosis lesion formation, specifically attachment of endometrial cells to peritoneal mesothelial cells (PMC) and invasion of endometrial cells through PMC (trans-mesothelial invasion). Raf-1 antagonist GW5074 decreased attachment to PMC and trans-mesothelial invasion by primary EEC and ESC. Raf-1 also mediated TGFβ-induced trans-mesothelial invasion by the established, low-invasive EEC line EM42. TGFβ treatment of EEC resulted in Raf-1 phosphorylation at S338 and phosphorylation of ERK, suggesting that TGFβ activates Raf-1 signaling in these cells. GW5074 had little effect on ESC proliferation but inhibited EEC growth significantly under reduced serum conditions. Antagonizing Raf-1 activity and expression via GW5074 and specific Raf-1 small interfering RNA, respectively, did not alter EEC resistance to growth inhibition by TGFβ. Raf-1 inhibition blocked induction of EEC growth by epidermal growth factor. Our data suggest that Raf-1 may mediate pathologic steps involved in early endometriosis lesion formation and may be a mediator of TGFβ and epidermal growth factor actions in endometriosis.     

Serum beta human chorionic gonadotropin levels can inform outcome counseling after in vitro fertilization

The predictive value of serum beta hCG level for fetal cardiac motion and pregnancy outcome after IVF was evaluated. The serum hCG level 12 days after ET is a useful predictor of subsequent presence of fetal cardiac activity and live birth and may assist clinicians in counseling patients regarding their IVF outcome.     

Inhibition of CD44 N- and O-linked glycosylation decreases endometrial cell lines attachment to peritoneal mesothelial cells

The attachment of endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs) to peritoneal mesothelial cells (PMCs) with and without inhibition of N- and O-linked glycosylation, the viability of EECs and ESCs, and the expression of CD44 surface density were evaluated. Inhibition of CD44 N- and O-linked glycosylation by using tunicamycin and/or B-GalNAc statistically significantly inhibited endometrial cell attachment to peritoneal mesothelial cells, suggesting a role in establishment of early endometriotic lesions.     

In vitro fertilization outcomes in Hispanics versus non-Hispanic whites

The in vitro fertilization (IVF) outcomes, including clinical intrauterine gestation rate and live birth rate, between Hispanic and non-Hispanic white women were compared, and there were no differences. Hispanics were more likely to have a diagnosis of tubal factor infertility, whereas non-Hispanic white women were more likely to have endometriosis as their infertility diagnosis.     

Response of mouse Lewis lung carcinoma to variation in dietary retinyl esters

The effect of manipulating dietary concentrations of retinyl acetate or retinyl palmitate on the growth of subcutaneous murine Lewis lung carcinoma was studied. Both deficiencies and excesses of vitamin A resulted in slowed tumor growth. An optimal intermediate level of dietary vitamin A for solid tumor growth was established. Although previous studies have suggested that established subcutaneous Lewis tumors were responsive to various forms of chemotherapy, a significant increase in the efficacy of BGNU therapy was observed when drug treatment was coupled with either deficient or excessive amounts of dietary retinyl esters.     

Etiology of infertility in monkeys with endometriosis: measurement of peritoneal fluid prostaglandins

To study the relationship between peritoneal fluid prostaglandins and infertility associated with endometriosis, we autografted endometrial or adipose tissue to the pelvic peritoneum in 21 monkeys. Peritoneal washings were collected prior to tissue transplantation and during a subsequent laparotomy performed for biopsy of the implants. Monkeys were mated and peritoneal washings were collected during three subsequent cycles. The content of prostaglandin F2 alpha (PGF2 alpha) in adipose tissue autografts was significantly less (p less than 0.05) than in endometrial tissue autografts. The PGF2 alpha concentration in peritoneal fluid increased significantly (p less than 0.05) only in monkeys that developed moderate or severe endometriosis. Prostaglandin E levels in tissue autografts or peritoneal fluid were similar in all animals. Infertility in monkeys with endometriosis was associated with luteinized unruptured follicles, luteal phase defects, and pelvic adhesions. Although PGF2 alpha concentrations in peritoneal washings obtained during these cycles were increased in comparison with those of ovulatory cycles, the difference was not significant. A relationship between spontaneous abortion and prostaglandin concentrations in peritoneal fluid was not established.     

Responses of an experimental solid tumour to irradiation: A comparison of modes of fractionation.

Several radiotherapeutic schedules compatible with continued structural-functional integrity of the gastrointestinal (GI) mucosa were compared utilizing the P815X2 murine mastocytoma grown as a solid subcutaneous tumour. Both the tumour and underlying normal tissues were irradiated during the treatments. The tumour exhibited a Do that increased from 210 rad to 397 rad as the tumour aged and in all instances demonstrated minimal shoulders in survival curves. In spite of a relative radioresistance of cells within the solid tumour, quite effective control of localized disease could be accomplished with radiotherapy schemes compatible with GI tolerance limits. Schedules evaluated utilizing this model included acute exposures to 1122 rad, daily exposure to 187 rad, 5 days/week exposures to 281 rad, twice weekly exposures (561 rad on Mondays and 374 rad on Thursdays) and a high dose, two fractions per day, schedule. Tumours were followed for changes in growth patterns during these schedules. Efficacy of tumour control was determined and schedules were compared on this basis. Aggressive radiotherapy approaching the tolerance limits of any of the fractionation schemes proved most effective.     

Plasma cell granuloma of the thyroid

Plasma cell infiltrates in the thyroid are rare. They may represent several processes, such as localized plasmacytoma, multiple myeloma, or plasma cell granuloma (PCG). It may be difficult to distinguish these disorders on the basis of morphologic features in sections stained with hematoxylin-eosin. All may be composed of mature plasma cells, without admixed macrophages or lymphocytes, that infiltrate the thyroid and adjacent connective tissue. The identification of the uncommon, but benign, PCG is facilitated by immunohistochemical staining to demonstrate an admixture of plasma cells with cytoplasmic kappa and lambda light chains. The polyclonal nature of the plasma cell infiltrate distinguishes PCG from neoplastic plasma cell proliferation.