Pregnancy Derived Compounds that Control Proliferation

Barnea, Eytan R.; Aboagye-Mathiesen, George; Hatch, William C.; Leavis, Paul C.

doi:10.1007/978-1-4471-0707-1_22

Cited by 4 publications

(4 citation statements)

References 40 publications

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“…Pregnancy is a unique immune state, a "perfect transplant" in which there is no host-versus-graft (motherversus-embryo) immune reaction, or, conversely, graft-versus-host (embryo-versus-mother) reaction, despite the semiallogeneity or total allogeneity of the fetus [9,14,34]. Moreover, pregnant women do not experience immune suppression, as evidenced by their maintained, adaptive, and strengthened as-needed ability to fight cancer and immune disorders (eg, leukemia, multiple sclerosis) [11,20]. We previously reported that PIF, an embryo-derived peptide, plays a determining role in creating this maternal immune tolerance toward the embryo, as well as promoting implantation [21,23].…”

Section: Discussionmentioning

confidence: 99%

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PreImplantation Factor Reduces Graft-versus-Host Disease by Regulating Immune Response and Lowering Oxidative Stress (Murine Model)

Azar

Shainer

Almogi-Hazan

et al. 2013

Biology of Blood and Marrow Transplantation

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Bone marrow transplantation (BMT) to treat severe hematologic malignancies often leads to potentially fatal acute graft-versus-host disease (GVHD), despite attempts at better donor-recipient matching and/or use of immunosuppressive agents. We report that embryo-derived PreImplantation Factor (PIF) plays a determining role in developing maternal/host tolerance toward the semiallogeneic or total allogeneic embryo and in regulating systemic immune response. Synthetic PIF treatment has proven effective in preventing immune attacks in nonpregnant models of autoimmunity. In this study, we tested the capability of PIF to prevent the development of acute GVHD in semiallogeneic or totally allogeneic murine BMT models. We examined the regulatory effect of PIF both in vivo and in vitro to control deleterious GVHD while maintaining its ability to preserve the beneficial graft-versus-leukemia (GVL) effect. Bone marrow and spleen cells from C57BL/6 donors were transplanted in semiallogeneic (C57BL/6xBALB/c) F1 or allogeneic (BALB/c) mice, which were then treated with PIF 1 mg/kg/day for 2 weeks. Short-term PIF administration reduced acute GVHD in both models and increased survival for up to 4 months after semiallogeneic or totally allogeneic BMT. This effect was coupled with decreased skin inflammation (semiallogeneic model) and decreased liver inflammation (both models), as well as reduced colon ulceration (allogeneic model). GVHD-associated cytokine and chemokine gene expression were decreased in the liver. PIF further lowered circulating IL-17 levels, but not IFN-γ levels. Both in vivo and in vitro, PIF treatment was demonstrated to lead to decreased inducible nitric oxide synthase expression and decreased lipopolysaccharide-activated macrophages to lower nitric oxide secretion. Significantly, PIF did not diminish the beneficial GVL effect in the B cell leukemia model. PIF acts primarily by inducing the regulatory phenotype on monocytes/antigen-presenting cells, which controls T cell proliferation. Overall, our data demonstrate that PIF protects against semiallogeneic and allogeneic GVHD long term by reducing both target organ and systemic inflammation and by decreasing oxidative stress, while preserving the beneficial GVL effect.

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Section: Discussionmentioning

confidence: 99%

“…Some of these include modulated/regulatory immune cells, such as M2 macrophages and uterine natural killer (NK) cells [9,10]. Thus, the immunologic profile of pregnancy is compatible with that of the desired GVHD prophylaxis [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

PreImplantation Factor Reduces Graft-versus-Host Disease by Regulating Immune Response and Lowering Oxidative Stress (Murine Model)

Azar

Shainer

Almogi-Hazan

et al. 2013

Biology of Blood and Marrow Transplantation

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“…In reviewing the situation with PIF and other early factors, Barnea [79] pointed out that the embryo-maternal dialogue starts shortly after fertilization and is exerted through both local and systemic signaling. First comes the PIF, secreted in humans already at the 2-4-cell stage, that initiates the modulation of cellular immunity.…”

Section: Factors Predictive Of Embryonic Loss the Embryo-maternal Dia...mentioning

confidence: 99%

Events Leading to the Establishment of Pregnancy and Placental Formation: The Need to Fine-Tune the Nomenclature on Pregnancy and Gestation

Benagiano,

Mancuso,

Guo

et al. 2023

IJMS

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Today, there is strong and diversified evidence that in humans at least 50% of early embryos do not proceed beyond the pre-implantation period. This evidence comes from clinical investigations, demography, epidemiology, embryology, immunology, and molecular biology. The purpose of this article is to highlight the steps leading to the establishment of pregnancy and placenta formation. These early events document the existence of a clear distinction between embryonic losses during the first two weeks after conception and those occurring during the subsequent months. This review attempts to highlight the nature of the maternal–embryonic dialogue and the major mechanisms active during the pre-implantation period aimed at “selecting” embryos with the ability to proceed to the formation of the placenta and therefore to the completion of pregnancy. This intense molecular cross-talk between the early embryo and the endometrium starts even before the blastocyst reaches the uterine cavity, substantially initiating and conditioning the process of implantation and the formation of the placenta. Today, several factors involved in this dialogue have been identified, although the best-known and overall, the most important, still remains Chorionic Gonadotrophin, indispensable during the first 8 to 10 weeks after fertilization. In addition, there are other substances acting during the first days following fertilization, the Early Pregnancy Factor, believed to be involved in the suppression of the maternal response, thereby allowing the continued viability of the early embryo. The Pre-Implantation Factor, secreted between 2 and 4 days after fertilization. This linear peptide molecule exhibits a self-protective and antitoxic action, is present in maternal blood as early as 7 days after conception, and is absent in the presence of non-viable embryos. The Embryo-Derived Platelet-activating Factor, produced and released by embryos of all mammalian species studied seems to have a role in the ligand-mediated trophic support of the early embryo. The implantation process is also guided by signals from cells in the decidualized endometrium. Various types of cells are involved, among them epithelial, stromal, and trophoblastic, producing a number of cellular molecules, such as cytokines, chemokines, growth factors, and adhesion molecules. Immune cells are also involved, mainly uterine natural killer cells, macrophages, and T cells. In conclusion, events taking place during the first two weeks after fertilization determine whether pregnancy can proceed and therefore whether placenta’s formation can proceed. These events represent the scientific basis for a clear distinction between the first two weeks following fertilization and the rest of gestation. For this reason, we propose that a new nomenclature be adopted specifically separating the two periods. In other words, the period from fertilization and birth should be named “gestation”, whereas that from the completion of the process of implantation leading to the formation of the placenta, and birth should be named “pregnancy”.

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“…Finally, metastasis of cancer from the mother to the fetus is extremely rare. 25 This indicates that pregnancy is actually "cancer protective," and the identification of specific compounds that are involved could be utilitarian. 26 This premise has led to studies to examine the sPIF effect in cancer using clinically relevant models.…”

Section: Introductionmentioning

confidence: 99%

PreImplantation Factor immunohistochemical expression correlates with prostate cancer aggressiveness

et al. 2020

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Background: The PreImplantation Factor (PIF)—a peptide secreted by viable embryos—exerts autotrophic protective effects, promotes endometrial receptivity and controls trophoblast invasion. Synthetic PIF (sPIF) has both immune-protective and regenerative properties, and reduces oxidative stress and protein misfolding. PIF is detected by immunohistochemistry (IHC) in hyperplastic endometriotic lesions and advanced uterine cancer. sPIF reduces graft-versus-host disease while maintaining a graft-versus-leukemia effect. Methods: PIF detection in prostate cancer was assessed in 50 human prostate samples following radical prostatectomy using tumor-microarray-based IHC correlating PIF immune staining with Gleason score (GS) and cancer aggressiveness. Results: PIF was detected in moderate-to-high risk prostate cancer (GS 4+3 and beyond, prognostic groups 3 to 5). In prostate cancer (GS (WHO Grade Group (GG)5), PIF was detected in 50% of cases; in prostate cancer (GS 4+4 GG4), PIF was observed in 62.5% of cases; in prostate cancer (GS 4+3 GG3), PIF immunostaining was observed in 57.1% of cases. In prostate cancer, (GS 3+4 GG2) and (GS 3+3 GG1) cases where PIF staining was negative to weak, membranous staining was observed in 20% of cases (staining pattern considered negative). High-grade prostate intraepithelial neoplasia PIF positive stain in 28.57% of cases (6 of 21) was observed. In contrast, PIF was not detected in normal prostate glands. Importantly, sPIF added to the PC3 cell line alone or combined with prostate cancer fibroblast feeder-cells did not affect proliferation. Only when peripheral blood mononuclear cells were added to the culture, a minor increase in cell proliferation was noted, reflecting local proliferation control. Conclusions: Collectively, PIF assessment could be a valuable, simple-to-use immunohistochemical biomarker to evaluate aggressiveness/prognosis in specimens from prostate cancer patients.

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Pregnancy Derived Compounds that Control Proliferation

Cited by 4 publications

References 40 publications

PreImplantation Factor Reduces Graft-versus-Host Disease by Regulating Immune Response and Lowering Oxidative Stress (Murine Model)

PreImplantation Factor Reduces Graft-versus-Host Disease by Regulating Immune Response and Lowering Oxidative Stress (Murine Model)

Events Leading to the Establishment of Pregnancy and Placental Formation: The Need to Fine-Tune the Nomenclature on Pregnancy and Gestation

PreImplantation Factor immunohistochemical expression correlates with prostate cancer aggressiveness

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