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Diana Prus

Publications and source records attributed to Diana Prus.

12 recordsLinked to original sources
PubMed2006

Decidual NK cells regulate key developmental processes at the human fetal-maternal interface.

Human CD56(bright) NK cells accumulate in the maternal decidua during pregnancy and are found in direct contact with fetal trophoblasts. Several mechanisms have been proposed to explain the inability of NK cells to kill the semiallogeneic fetal cells. However, the actual functions of decidual NK (dNK) cells during pregnancy are mostly unknown. Here we show that dNK cells, but not peripheral blood-derived NK subsets, regulate trophoblast invasion both in vitro and in vivo by production of the interleukin-8 and interferon-inducible protein-10 chemokines. Furthermore, dNK cells are potent secretors of an array of angiogenic factors and induce vascular growth in the decidua. Notably, such functions are regulated by specific interactions between dNK-activating and dNK-inhibitory receptors and their ligands, uniquely expressed at the fetal-maternal interface. The overall results support a 'peaceful' model for reproductive immunology, in which elements of innate immunity have been incorporated in a constructive manner to support reproductive tissue development.

Angiogenesis Inducing Agents↗
PubMed2006

The pattern of Protease Activated Receptor 1 (PAR1) expression in endometrial carcinoma.

OBJECTIVE: Protease Activated Receptors (PARs) form a family of G-protein-coupled proteins uniquely activated by proteolytic cleavage. While the role of either soluble or matrix-immobilized protease in tumor invasion is well established, the part of cell surface PARs is beginning to emerge. We sought to investigate the expression pattern of Protease Activated Receptor 1 (hPar1) in endometrial carcinoma, the most common type of gynecological malignancy. METHODS: Tissue biopsy specimens taken from seventy-four formalin-fixed, paraffin-embedded endometrial tissue blocks were obtained from archival material. Analysis of PAR1 expression was evaluated by riboprobe in situ hybridization for detection of RNA and immunohistochemistry techniques for localization of protein. Histological scoring was performed. RESULTS: The levels of hPar1 mRNA and protein were high and abundant in high-grade endometrial carcinoma, regardless of the histological subtype. In contrast, no hPar1 was detected in endometrial epithelia with conserved glandular structure represented by normal, hyperplastic or low-grade carcinomas. CONCLUSIONS: PAR1 over-expression is selectively confined to the highly aggressive, high-grade endometrial carcinoma and absent in tissue obtained from benign endometrium or low-grade endometrial cancer. This finding highlights the significance of hPar1 gene involvement in invasive endometrial carcinoma and appoints it an attractive candidate for anti-cancer therapy.

Biomarkers, Tumor↗
PubMed2005

Expression and regulation of Sprouty-2 in the granulosa-lutein cells of the corpus luteum.

Growth factor signalling has important modulatory roles in the process of human follicular growth, oocyte maturation and corpus luteum (CL) formation. Recently, Sprouty-2, an inhibitor of receptor tyrosine kinase (RTK) signalling pathway was advocated as a marker of oocyte competence in the bovine ovary. We sought to study Sprouty-2 expression and regulation in the human ovary. RT-PCR was used to detect Sprouty-2 mRNA in human granulosa-lutein cells (GLC) collected from follicular aspiration of IVF patients. The effect of epidermal and fibroblast growth factors (EGF and FGF) on Sprouty-2 mRNA expression in GLC was studied using quantitative real-time PCR. Immunohistochemistry was performed on cultured GLC, human CL and stimulated rat ovary sections. Sprouty-2 mRNA was expressed in human GLC. EGF and basic FGF, but not FGF4 and FGF10, increased Sprouty-2 mRNA expression in GLC. The Sprouty protein was localized to GLC of early and late human CL but not to the theca cell layer. Immunostaining of developing rat CL confirmed the temporal and spatial expression of Sprouty in humans. The detection of Sprouty-2 mRNA and protein in human GLC may suggest a role for Sprouty-2 during the final stages of follicle maturation and CL formation.

Adolescent↗
PubMed2005

Expression of serum amyloid A, in normal, dysplastic, and neoplastic human colonic mucosa: implication for a role in colonic tumorigenesis.

Serum amyloid A (SAA) is an acute phase reactant, whose level in the blood is elevated in response to trauma, infection, inflammation, and neoplasia. Elevated levels of SAA in the serum of cancer patients were suggested to be of liver origin rather than a tumor cell product. The role of SAA in human malignancies has not been elucidated. We investigated the expression of SAA at various stages of human colon carcinoma progression. Nonradioactive in situ hybridization applied on paraffin tissue sections from 26 colon cancer patients revealed barely detected SAA mRNA expression in normal looking colonic epithelium. Expression was increased gradually as epithelial cells progressed through dysplasia to neoplasia. Deeply invading colon carcinoma cells showed the highest levels of SAA. Expression was also found in colon carcinoma metastases. Cells of lymphoid follicles of the intestinal wall, inflammatory cells, ganglion cells, and endothelial cells, also expressed SAA mRNA. Immunohistochemical staining revealed SAA protein expression that colocalized with SAA mRNA expression. RT-PCR analysis confirmed the expression of the SAA1 and SAA4 genes in colon carcinomas, expression that was barely detectable in normal colon tissues. These findings indicate local and differential expression of SAA in human colon cancer tissues and suggest its role in colonic tumorigenesis.

Adenocarcinoma↗
PubMed2005

Spatiotemporal expression of heparanase during human and rodent ovarian folliculogenesis.

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs), major components of the basement membrane (BM) and extracellular matrix (ECM). Heparanase activity results in release of HSPG-bound molecules, including basic fibroblast growth factor (FGF2). Structural and functional development of the corpus luteum (CL) involves tissue remodeling, active angiogenesis, and steroid production. Heparanase-induced ECM and BM breakdown as well as FGF2-stimulated endothelial proliferation may have an important role in the regulation of luteal function. Heparanase mRNA was detected by reverse-transcription-polymerase chain reaction in granulosa cells recovered from follicular fluid of in vitro fertilization patients. Using sulfate-labeled ECM, heparanase enzymatic activity was determined in human luteinized granulosa cells. Employing immunohistochemistry, heparanase protein was localized predominantly in the theca interna cell layer of the mature antral follicle, whereas in human corpora lutea, both luteinized granulosa and theca cells were immunostained for heparanase. During luteolysis, heparanase was identified in macrophages surrounding the forming corpus albicans. In serially sectioned ovaries from unstimulated rats as well as from eCG-treated rats, expression of heparanase was noted exclusively in the ovarian steroid-producing interstitial tissue. Following an ovulatory dose of hCG, heparanase was immunostained also in lutein cells of the forming corpora lutea. Temporal expression of heparanase in granulosa cells during the luteal phase and in macrophages during luteal regression supports the hypothesis that heparanase plays a role in human ovarian ECM remodeling and may potentiate cellular migration and growth factor bioavailability.

Adolescent↗
PubMed2004

Clinical profile of breast cancer in Arab and Jewish women in the Jerusalem area.

BACKGROUND: The clinical profile of breast cancer may vary among different ethnic groups living in the same country and therefore affect the yield of a breast cancer screening program. The present study attempts to better characterize the breast cancer clinical profile of Arab women compared with Jewish women in the greater Jerusalem area with a future aim of establishing a comprehensive and effective screening program for this population. METHODS: Retrospective chart review was conducted and the following covariates were correlated with survival: ethnicity, age at diagnosis, and American Joint Committee on Cancer (TNM) stage at diagnosis. RESULTS: A total of 312 women were operated on for breast cancer between 1994 and 1999; 51% were Ashkenazi Jews (AJ), 26% were Sephardic Jews (SJ), 21% were Palestinian Arabs (PA), and 2% patients did not fit into those ethnic groups. The mean age at diagnosis was 51.5 years for the PA group, 53.4 +/- 1.5 for the SJ group, and 55.9 years for the AJ group (P <0.03 PA versus AJ). The tumor size (mean +/- SEM) was 38.8 +/- 3.7 mm, 31.1 +/- 2.4 mm, and 24.5 +/- 1.6 mm for the PA, SJ, and AJ groups, respectively (P = 0.03 for PA versus SJ and P <0.001 for PA versus AJ). Five-year overall survival was 77 %, 72%, and 58% for the AJ, SJ, and PA groups, respectively (P = 0.02); and 5-year disease-free survival was 72%, 51%, and 50% for the AJ, SJ, and PA groups, respectively (P = 0.03, AJ versus SJ). CONCLUSIONS: Our data demonstrate younger age and larger primary tumor size for the Arab patients compared with the Jewish patients. These findings were associated with lower 5-year survival and disease-free survival of the Arab patients.

Adult↗
PubMed2003

CXCL12 expression by invasive trophoblasts induces the specific migration of CD16- human natural killer cells.

In the maternal decidua, natural killer (NK) cells, characterized by lack of CD16, are found in direct contact with the fetal extravillous trophoblasts (EVTs). It is yet unknown which factors contribute to the specific homing of this unique NK subset to the decidua. In this study we analyze the chemokine receptor repertoire on various NK populations derived from the peripheral blood and decidua. We show that CXCR4 and CXCR3 receptors are preferentially expressed on CD16- NK subsets derived either from the peripheral blood or the decidua and that these receptors are involved in migration of all NK subsets to their ligands. We further demonstrate in vivo that invading EVTs that eventually perform endovascular invasion express CXCL12, the ligand for CXCR4, but not ligands for CXCR3. Indeed, specific accumulation of the CD16- NK cells at the expense of CD16+ cells was observed only when in vitro migration was performed with ligands for CXCR4. Finally, incubation of the peripheral blood CD16- NK cells with cytokines present in the decidua, especially interleukin 15 (IL-15), resulted in the expression of chemokine receptor repertoire similar to that observed on decidual NK cells, suggesting an additional important regulatory effect of local decidual cytokines.

Blood Vessels↗
PubMed2003

Mucosal melanoma of the female genital tract is a multifocal disorder.

OBJECTIVE: This is a retrospective analysis of malignant melanoma of the female genital tract, focusing on the high local recurrence rate of this tumor. METHODS: All women treated for malignant melanoma of the genital tract were identified through the archives of the Hadassah University Hospital. The medical records and the pathological specimens were reviewed and reevaluated. RESULTS: From 1986 to 2002, nine cases were diagnosed and treated at Hadassah. Seven had vulvar melanoma and two had vaginal melanoma. Sixty-six percent (6/9) of the patients had more than one focus of melanoma, either apparent at their initial diagnosis (3/9) or developed during follow up (3/9). Most of the recurring lesions were melanoma in situ. In one patient multiple nodular melanomas were detected. Atypical melanocytic hyperplasia was found in an otherwise normal mucosa in four patients. Three had experienced multiple recurrences. All patients were treated by radical local excisions with (3/9) or without (6/9) elective groin lymph node dissection. Three patients with locally recurring melanoma within the genital tract required two to five sessions of repeated surgical excisions. CONCLUSION: It is suggested that melanoma of the genital tract is the result of a multifocal disorder of the melanocytes within the mucosa. The increased local recurrence rate reflects an inherent abnormality of melanocytes. It is not attributed to surgical failure in controlling the disease. Insistent and even radical surgical excision is recommended, especially for patients whose prospects for prolonged survival are improved.

Adult↗
PubMed2002

A primary immunodeficiency disorder associated with absence of lymphoid germinal centers.

In this article we describe three infants who suffered from a disorder characterized by splenomegaly, anemia, and severe infections beginning during the first months of life. Immunologic studies revealed agammaglobulinemia. However, normal numbers of lymphocytes and lymphocyte subsets were present in peripheral blood, and lymphocyte proliferation in responses to mitogenic stimulation in vitro was normal. Histologic and immunohistologic studies performed in one of the patients revealed lack of secondary follicles and follicular dendritic cells in lymphoid tissues and absence of plasma cells in the intestinal lamina propria. Similar findings have been observed in the hyper-IgM syndrome. However, these patients can be distinguished from currently recognized genetic variants of hyper-IgM syndrome on the basis of their clinical and histologic features, together with information obtained from DNA sequence analysis. Thus, their condition is likely to represent a novel form of primary immune deficiency with features of hyper-IgM syndrome.

Agammaglobulinemia↗
PubMed2002

Impact of repeated testicular fine needle aspirations (TEFNA) and testicular sperm extraction (TESE) on the microscopic morphology of the testis: an animal model.

BACKGROUND: The aim of this work was to compare testicular histological changes occurring following testicular fine needle aspiration (TEFNA) and testicular sperm extraction (TESE). METHODS: TESE or TEFNA were performed on normal male rats, in a similar manner to azoospermic men. The animals were killed after 7, 14 and 31 days and their testes were examined. RESULTS: TESE caused chronic inflammation, occasional necrosis and degenerative changes in testicular germ cells in only approximately 10% of the remaining testicular tissue. TEFNA caused widespread architectural distortion of seminiferous tubules into irregular and deformed lumens lined by Sertoli cells only, as well as focal chronic inflammation, necrosis and degenerative changes accompanied by decreased spermatogenesis. Similar but less extensive changes were noted when fewer punctures were performed. When negative suction pressure was not applied during TEFNA, similar histological changes occurred, indicating that testicular damage was related to the puncture itself. Following either procedure, the contralateral non-operated testes were unaffected. CONCLUSION: In this animal model, TEFNA inflicts severe, progressive and irreversible damage on the architecture of the tubules in the needle's path. The multi-focal nature of this technique eventually leads to widespread tubular atrophy that is proportional to its extent. In contrast, TESE causes localized scarring and fibrosis, rendering most of the remaining testicle intact. The clinical relevance of such findings, produced in normal animal testes, to testes of azoospermic men, is yet to be determined.

Animals↗
PubMed2002

Localization of heparanase in normal and pathological human placenta.

Degradation of extracellular matrix (ECM) components is critical for invasion. Heparan sulphate proteoglycans are abundant in the ECM of the placenta and the decidua, hence their degradation may disassemble the matrix and facilitate placentation and trophoblast invasion. This study investigates the expression of heparanase in normal and pathological placentation using RT-PCR, in-situ hybridization and immunohistochemistry analysis to detect heparanase in specific cells of the placenta and at the fetal-maternal interface throughout pregnancy. Heparanase was observed in villous cytotrophoblasts (CT), syncytial trophoblasts (ST) and in intermediate trophoblast cell columns in normal first trimester, molar and ectopic pregnancies. The heparanase protein was preferentially expressed in the endothelium of fetal capillaries, and to a much lesser extent in larger fetal vessels. Extravillous trophoblasts (EVT) invading the decidua and the maternal vessels were also heparanase positive. In the second and third trimesters, villous CT remained heparanase positive whereas ST showed variable heparanase expression. EVT invading the placental implantation site were also positively stained. A similar pattern was observed in samples obtained from pre-eclamptic placentae and from placenta accreta. Our results indicate consistent expression of heparanase in normal and abnormal placenta, in small fetal vessels and in a variety of trophoblast subpopulations with different invasive potentials.

Female↗