33 research outputs found
Polymorphisms in VEGF and KDR genes in the development of endometriosis: a systematic review
Abstract Objectives: to review studies that used case-control design to verify the association of polymorphisms in VEGF an
Anticancer potential, molecular mechanisms and toxicity of Euterpe oleracea extract (açaÃ): A systematic review.
Cancer is an increasingly frequent malignancy worldwide, and despite the advances in drug development, it is still necessary to develop new plant-derived medicines. Euterpe oleracea (açaÃ) is abundant in South and Central America and has health benefits due to its high levels of phytochemicals, including lignans and polyphenols. The aim of this review was to systematically describe the safety and antitumor effects of açaà in preclinical models using rodents to provide a more comprehensive assessment of açaà for both therapeutic uses and the development of future clinical studies in cancer. Eligible studies were identified using four international databases (PubMed, Medline, Lilacs and SciELO) from their inception date through December 2017. The included studies were analyzed with methodological rigor (QATRS) to enable better quality control for these experimental studies. Sixty publications were identified in the databases, but only 9 articles were eligible: 6 evaluated the pharmacological effects of açaà in animal models of cancer (1 model each of esophageal cancer, urothelial cancer, melanoma and Walker-256 tumor and 2 models of colon cancer), and 3 were toxicological assays using preclinical models with rodents. Overall, 747 animals were analyzed. On a QATRS score scale of 0-20, the quality of the studies ranged from 16 to 20 points. Pulp was the main fraction of açaà administered, and an oral administration route was most common. The açaà dosage administered by gavage ranged from 30 mg/kg to 40,000 mg/kg, and açaà fed in the diet accounted for 2.5% to 5% of the diet. The anticarcinogenic and chemopreventive activities of açaà were observed in all experimental models of cancer and reduced the incidence, tumor cell proliferation, multiplicity and size of the tumors due to the antiinflammatory, antiproliferative and proapoptotic properties of açaÃ. No genotoxic effects were observed after açaà administration. The results of this review suggest that açaà is safe and can be used as a chemoprotective agent against cancer development. Açaà therapy may be a novel strategy for treating cancer
Vascular density and distribution of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) are significantly higher in patients with deeply infiltrating endometriosis affecting the rectum
Objective: To analyze vascular density and immunolocalization of angiogenic vascular endothelial growth factor (VEGF) and its receptor Flk-1 in the proliferative and secretory eutopic human endometrium. and in three different sites of endometriosis: the ovary, bladder, and rectum. Design: Prospective study. Setting: University hospital. Patient(s): Thirty women with endometriosis (10 ovarian, 1.0 bladder, 10 rectal) and 32 control women (10 proliferative endometrium, 10 secretory endometrium, 4 normal ovary, 4 normal bladder, 4 normal rectum). Intervention(s): Normal endometrial samples were obtained from women during laparoscopic ablation of subserous myoma, and biopsy specimens of endometriosis were obtained from patients undergoing surgery for the diagnosis and treatment of endometriosis. Normal tissues of ovary, bladder, and rectum were obtained from these organs beside the lesions of endometriosis. Main Outcome Measure(S): Blood vessels were quantified according to the number of von Willebrand factor-positive endothelial cells. The VEGF and Flk-1 distribution were evaluated semiquantitatively by immunohistochemical staining. Result(s): More blood vessels were found in cases of endometriosis, particularly rectal endometriosis, compared with the respective control samples and with the eutopic endometrium, and they were localized in endometrial stroma around the glands. The VEGF and Flk-1 expression levels were also higher in cases of endometriosis, especially rectal endometriosis. Conclusion(s): Vascularization and VEGF and Flk-1 expression are significantly higher in deeply infiltrating endometriosis affecting the rectum, reinforcing the hypothesis that antiangiogenesis therapy may constitute a new modality of treatment, especially in cases of deep endometriosis involving the rectum
Polymorphisms in VEGF and KDR genes in the development of endometriosis: a systematic review
Abstract Objectives: to review studies that used case-control design to verify the association of polymorphisms in VEGF and KDR genes in the development of endometriosis. Methods: the systematic review selected articles published until September 1, 2015 from PubMed, MEDLINE, BVS, SciELO databases, considering the following key words: endometriosis and ("polymorphism" or "SNP" or "genetic polymorphism") and ("VEGF" OR "Vascular endothelial growth factor" or "VEGFR-2" or "Vascular endothelial growth factor-2" or "KDR" or "Kinase Insert Domain Receptor"). Results: 106 articles were identified, only 11 were eligible. Discrepant results were observed regarding polymorphisms in VEGF gene in the development of endometriosis, which can be explained by methodological differences, sample size, eligible control type, using the unadjusted risk estimates and the heterogeneity of the studied population. Only one study investigated polymorphisms in KDR gene in the development of endometriosis, however it was ineligible for this review. Conclusions: to avoid discrepancy in the results, we suggest that the ideal control group should be formed by fertile women and free of gynecological diseases. Multicentric studies with adequate design, involving different population besides the combined analysis on polymorphisms in VEGF and KDR genes are still necessary to contribute in the understanding of this disease, which are social, clinical and economical problems
Schematic representation of the effects of açaà on tumor cells.
<p>Açaà was shown to have antitumoral functions due its antiinflammatory, antiproliferative and proapoptotic properties.</p
Basic information on the <i>in vivo</i> experimental models used to test the effects of <i>E</i>. <i>oleracea</i>.
<p>Basic information on the <i>in vivo</i> experimental models used to test the effects of <i>E</i>. <i>oleracea</i>.</p
A GFP endometriosis model reveals important morphological characteristics of the angiogenic process that govern benign and malignant diseases
Endometriosis involves the growth of
endometriotic tissue outside the uterine cavity, and is
frequently associated with different malignancies. A
well-reported alteration in the disease microenvironment
is the proliferation of new blood vessels around the
lesions, as part of a necessary repertory to contribute to
the invasiveness and development of infiltrating
endometriosis. Therefore, the establishment of a reliable
experimental model is essential to elucidate the
contribution of angiogenesis and to develop new
therapeutic approaches to endometriosis treatment. For
this purpose we transplanted endometrial fragments from
green fluorescent protein (GFP)-mice (n=20) into the
peritoneal cavity of wild-type mice (n=20), and then
analyzed the morphological changes and the process of
angiogenesis. The lesions were cystic and vascularized,
and showed morphological hallmarks such as
endometrial glands and stroma. An increase in
endometriotic lesion vascular density was revealed by
immunostaining and RNAm expression for Vegf and its
receptor Flk-1, and the lesions were confirmed as a
tissue-donor source by GFP fluorescent cells. The same
pattern was observed through staining of activated
macrophages and an increase of about 25% in the
number of macrophage-positive cells was also
demonstrated in endometriotic lesions by flow
cytometry, which concords with previous data that
correlate endometriosis, angiogenesis and inflammation.
According to our understanding, this is the first
demonstration that the pattern of the angiogenic process
in the GFP endometriosis model is very similar to that of
cancer. These observations will be useful for
investigation of the process of angiogenesis involved in
the attachment and invasion of endometrial cells, as well
as an in vivo platform model to study the effects of
antiangiogenic drugs