SUSD2 expression in high-grade serous ovarian cancer correlates with increased patient survival and defective mesothelial clearance.

The cause of death among the majority of epithelial ovarian cancer (EOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Thus, it is important to identify the factors that mediate EOC metastasis and implantation, including clearance of the mesothelium. Sushi domain containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Immunohistochemical analysis determined the presence of SUSD2 in several subtypes of EOC, with the strongest staining observed in high-grade serous ovarian carcinomas (HGSOCs). A high-density, clinically annotated HGSOC tissue microarray was stained with an anti-SUSD2 antibody. Patients with tumors that had a low percentage of SUSD2 staining cells had a shorter median survival (31.7 months) compared with patients who had tumors with extensive SUSD2 staining (49.1 months; P-value=0.0083). To investigate the role of SUSD2 in HGSOCs, stable OVCAR3, OVSAHO and KURAMOCHI cell lines were established with knockdown (KD) or non-targeting (NT) of SUSD2. Boyden chamber and wound-healing assays demonstrated that OVCAR3, OVSAHO and KURAMOCHI SUSD2-KD cells migrated at significantly higher rates compared with their SUSD2 NT counterpart cell lines. Quantitative reverse transcription-PCR and western immunoblot analysis indicated an inverse relationship between SUSD2 and well-characterized mesenchymal proteins, including Twist-1, Zeb-1, N-cadherin, STEAP1, AHNAK, Snail-1, COL5A2 and Snail-3 in OVCAR3, OVSAHO and KURAMOCHI cell line models. In addition, OVCAR3 and KURAMOCHI SUSD2-KD spheroids displayed increased mesothelial clearance ability compared with cells that express endogenous levels of SUSD2. These data suggest that SUSD2 has a role in the inhibition of mesothelial clearance, which is required for metastasis. Altogether, our findings indicate that SUSD2 impedes migration, epithelial-to-mesenchymal transitional and mesothelial clearance of HGSOC cells, consistent with prolonged survival of patients with SUSD2-expressing tumors.

Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes.

The antigenic polymorphism of HIV-1 is a major obstacle in developing an effective vaccine. Accordingly, we screened random peptide libraries (RPLs) displayed on phage with antibodies from HIV-infected individuals and identified an array of HIV-specific epitopes that behave as antigenic mimics of conformational epitopes of gp120 and gp41 proteins. We report that the selected epitopes are shared by a collection of HIV-1 isolates of clades A-F. The phage-borne epitopes are immunogenic in rhesus macaques, where they elicit envelope-specific antibody responses. Upon intravenous challenge with 60 MID50 of pathogenic SHIV-89.6PD, all monkeys became infected; however, in contrast to the naive and mock-immunized monkeys, four of five mimotope-immunized monkeys experienced lower levels of peak viremia, followed by viral set points of undetectable or transient levels of viremia and a mild decline of CD4+ T cells, and were protected from progression to AIDS-like illness. These results provide a new approach to the design of broadly protective HIV-1 vaccines.

[Intrauterine therapy with levonorgestrel releasing IUD of women with hypermenorrhea secondary to uterine fibroids]. / Wewnatrzmaciczna terapia levonorgestrelem obfitych miesiaczek spowodowanych miesniakami macicy--doniesienie wstepne.

OBJECTIVES: The aim of the study was to evaluate the effectiveness of Mirena IUD (Schering) treatment in women with severe menstrual bleedings secondary to uterine fibroids. MATERIAL AND METHODS: The study comprised 12 women in the age of 30 to 43 years (average 36.4) with uterine fibroids and severe menstrual bleedings. Eight patients developed anemia with hemoglobin levels below 12 g/dL. All women were treated with the levonorgestrel releasing IUD. Half of the group was observed for 6, and the remaining women for 12 months. Intensity of menstrual bleedings was evaluated prior and after the treatment. US evaluation comprised measurements of endometrium and the fibroids. RESULTS: No early complications were observed following the insertion of the IUD. Six weeks following the insertion, one patient had persisted menstrual bleedings and was operated, the remaining 11 noted decrease in the intensity of menstruation. After twelve weeks 3 out of 6 women with intramural fibroids developed ammenorrhea, the remaining 3 had scanty menstrual bleedings. Hemoglobin levels were normal in 11 women already 6 months after the insertion of IUD. Post treatment US revealed endometrium thickness of no more then 4 mm, and no change in the fibroids volume. CONCLUSION: Insertion of levonorgestrel releasing Mirena IUD (Schering) reduces intensity of menstrual bleedings secondary to uterine fibroids.

[The value of hysterosalpingoscintigraphy in examining the patency and activity of oviducts]. / Wartosc histerosalpingoscyntygrafii w badaniu droznosci i czynnosci jajowodów.

As many as 15 patients have been examinedby hysterosalpingoscintigraphy by administration of albumin macroaggregates labelled with Te99m (HAMA) into posterior vaginal fornix and external orifice of uterine cervix. Gamma camera was used to observe the transportation of molecules through the cervical canal, uterine cavity as well as oviducts to peritoneal cavity. The results were compared with HSG examination and salpingochromotubation. is 93%. Hysterosalpingoscintigraphy allows us to estimate both the anatomical patients after reconstructive operations involving oviducts.

[Results of treating endometriosis with infertility using operative laparoscopy]. / Wyniki leczenia endometriozy wspólistniejacej z nieplodnoscia przy zastosowaniu laparoskopii operacyjnej.

In the work, the efficiency of treating endometriosis by hormonal as well as combined methods, and employing the operative laparoscopy was evaluated. The study involved 89 infertile women with endometriosis being of various grade of advancement. Sixty women underwent combined treatment according to Samm, the remaining 29 were given hormonal therapy with Danazol and Orgametril preparations. After combined treatment full recovery was obtained in 26.7% of cases, improvement in 40%, but after the use of preparations Orgametril, Organon or Danazol, Winthrop, complete cure was reached in 12.8% of cases, improvement in 31%. Only 8 women became pregnant after combined therapy. Complete recovery concerned mainly less advanced endometriosis, particularly following the combined treatment according to Semm. Early laparoscopic diagnosis increases the chance of curing endometriosis and fertility associated with it.

[Developmental anomalies of the uterus in a population of 3000 women with various causes of infertility]. / Wady rozwojowe macicy w zbiorowosci 3000 kobiet z rózna przyczyna nieplodnosci.

In the years from 1979 to 1991 a population of 3000 women with various causes of infertility was found to have in 13.34% developmental anomalies of uteri. As many as 9.27% consisted of saddle uteri, 2.67% bicornous, in 0.37% there was partial, and in 0.13% complete septum, in 0.57% unicornous and in 0.33% double. The diagnosis of developmental anomalies involving uterus was based mainly on HSG, laparoscopic and hysteroscopic examinations.

[Effect of hydrotubation on the anatomical state of oviducts in women with mechanical infertility]. / Wplyw hydrotubacji na stan anatomiczny jajowodów u kobiet z nieplodnoscia mechaniczna.

The aim of the paper was to evaluate the anatomical state of uterine adnexa in women operated on due to mechanical infertility. Hydrotubation were previously applied in 31 women stemming from various centres in the country, while in 31 such a treatment was not performed at all. The mentioned groups of women were encumbered, to a similar degree, with a risk factor of infertility, except for the duration of sterility, which in those treated by hydrotubation lasted on the average 2 years longer. From 5 to 50 hydrotubations were carried out, most frequently in series of 5 procedures. It was reported by the women that 8 of them after hydrotubation experienced hypogastric pain persisting for some days, and in 6 there was acute adnexitis. Destructive changes in uterine adnexa, being estimated during the reconstructive operation, were decidedly more advanced in women treated by hydrotubation. That was expressed mainly by frequent appearance of lytic adhesions as well as by more advanced fibrosis of oviducts, particularly that of endosalpinx. Unchanged oviducts, after their release from adhesions, also appeared less frequently.