The Effect of Rubus idaeus Polyphenols Extract in Induced Endometriosis in Rats.

Endometriosis is a common gynecological condition with a complex physio-pathological background. This study aimed to assess the role of Rubus idaeus leaf extract (RiDE) as a potential therapeutic agent in reducing the size of the endometriotic lesions and modulate the plasma expression of MMP-2, MMP-9, and TGF-ß1. The endometriotic lesions were induced in a rat model by the autologous transplant of endometrium. Thirty-six female rats, Wistar breed, with induced endometriosis, were divided into four groups and underwent treatment for 28 days. The CTRL group received 0.5 mL/day of the vehicle; the DG group received 1 mg/kg b.w./day dienogest; the RiDG group received 0.25 mL/kg b.w./day RiDE and the D+RiDG group received 1 mg/kg b.w./day dienogest and 0.25 mL/kg b.w./day RiDE, respectively. Rats' weight, endometriotic lesion diameter and grade, and plasma levels of MMP-2, MMP-9, and TGF-ß1 were assessed before and after treatment. The administration of RiDE in association with dienogest vs. dienogest determined a lower weight gain and a reduction in diameter of the endometriotic lesions. RiDE administration restored MMP2 and MMP9 plasma levels to initial conditions. Rubus idaeus extract may help in reducing dienogest-associated weight gain, lower the size of endometriotic lesions, and have anti-inflammatory effects through MMP2 and MMP9 reduction.

The Role of Circulating Tumor Cells in the Prognosis of Metastatic Triple-Negative Breast Cancers: A Systematic Review of the Literature.

Breast cancer is one of the leading causes of death in women worldwide. One subtype of breast cancer is the triple-negative, which accounts for 15% of total breast cancer cases and is known for its poor prognosis. The main cause of death is due to metastasis. Circulating tumor cells (CTCs) play a key role in the metastatic process. CTCs arise either by detaching from the primary tumor or from cancer stem cells undergoing an epithelial-to-mesenchymal transition (EMT). This review aims to present up-to-date data concerning the role of CTC numbers in relation to the prognostic and treatment response in metastatic triple-negative breast cancer (mTNBC) patients, and also to discuss the methods used for CTCs' identification. A search in the MEDLINE database was performed. A total of 234 articles were identified. The results of the 24 eligible studies showed that positive CTC status is associated with shorter overall survival (OS) and progression-free survival (PFS) in mTNBC patients. Furthermore, a decrease in number of CTCs during therapy seems to be a favorable prognostic factor, making CTCs' detection an important prognostic tool before and during therapy in mTNBC patients. The methods used for CTC detection are still developing and need further improvement.

Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis.

Vascular endothelial growth factor (VEGF) represents a growth factor with important pro-angiogenic activity, having a mitogenic and an anti-apoptotic effect on endothelial cells, increasing the vascular permeability, promoting cell migration, etc. Due to these effects, it actively contributes in regulating the normal and pathological angiogenic processes. In humans, the VEGF family is composed of several members: VEGF-A (which has different isoforms), VEGF-B, VEGF-C, VEGF-D, VEGF-E (viral VEGF), VEGF-F (snake venom VEGF), placenta growth factor (PlGF), and, recently, to this family has been added endocrine gland-derived vascular endothelial growth factor (EG-VEGF). VEGF binds to tyrosine kinase cell receptors (VEGFRs): VEGFR-1 [Fms-like tyrosine kinase 1 (Flt-1)], VEGFR-2 [kinase insert domain receptor (KDR) in human; fetal liver kinase 1 (Flk-1) in mouse] and VEGFR-3 [Fms-like tyrosine kinase 4 (Flt-4)]. While VEGFR-1 and VEGFR-2 are expressed predominantly on vascular endothelial cells, VEGFR-3 is expressed especially on lymphatic endothelial cells. VEGFR-2 has the strongest pro-angiogenic activity and a higher tyrosine kinase activity than VEGFR-1. Endothelial cells also express co-receptors, such as neuropilin-1 (NP-1) and neuropilin-2 (NP-2), which modulate tyrosine kinase receptor activity. Both VEGF and VEGFRs are expressed not only on endothelial cells, but also on non-endothelial cells. This article aims to highlight the most recent data referring to the VEGF family and its receptors, as well as its implications in the angiogenesis process. At present, blocking angiogenesis in cancer or in other pathological processes, using anti-VEGF and anti-VEGFRs therapies, is considered to be extremely important.

Highlighting the R1 and R2 VEGF receptors in placentas resulting from normal development pregnancies and from pregnancies complicated by preeclampsia.

Preeclampsia (PE), a pathological entity characterized by hypertension and pregnancy-related proteinuria, is a medical condition of incompletely known etiopathogenesis. Placental defects and placental angiogenesis may be a cause of this condition. The main factor that controls angiogenesis in the early stages of placental development is vascular endothelial growth factor A (VEGF-A) and its two receptors, namely VEGFR-1 and VEGFR-2. This study analyzed the immunohistochemical (IHC) expression of the two VEGF receptors, R1 and R2, in pregnancies complicated by PE compared to pregnancies with a normal evolution. The pregnancies included into the study for the harvesting of placental tissue to be microscopically analyzed were divided into two groups: the group of physiological pregnancies (22 pregnancies) and the group of pregnancies complicated by preeclampsia (13 pregnancies). For the microscopic analysis, we used the Hematoxylin-Eosin (HE), Masson's trichrome and IHC stainings. The microscopic aspects of HE and Masson's trichrome stainings most commonly found in normal development pregnancies underlie the normal process of placental senescence. In the case of pregnancies complicated by PE, the microscopic analysis of the placentas revealed fibrinoid necrosis of the vascular wall, lipid-loaded endothelial cells, diffuse trophoblastic hypertrophy, microinfarctions, calcification areas, fibrin deposits, vascular-syncytial membrane surface reduction, basement membrane thickening. According to the established marker intensity score, the VEGFR-1 and VEGFR-2 receptors were more pronounced in the placentas resulting from pregnancies complicated by preeclampsia. The present study brings arguments that support the major regulatory role of VEGF-A and of the two receptors in the normal or pathological angiogenesis in the placenta, and implicitly in the pathogenesis of preeclampsia. Further studies are needed for a more comprehensive analysis of the stages in which these factors cause alteration of the placental angiogenesis and vasculogenesis processes, so that they can intervene effectively in the treatment or prevention of this disease.