Breast cancer usually grows very quickly, becoming insensitive to blood flow in nearby veins; because of that, inside solid tumors it's possible to find a hypoxic environment, in other words, an environment where oxygen is less available. Another feature of cancer is its angiogenesis rate, because of the high energy demand, new blood vessels must be produced to take nutrients inside the solid tumor mass. Even with normal blood flow bringing the cancer oxygen and nutrients, its cells favor hypoxia, in an event known as Warburg Effect. According to the Warburg Effect, cells, even with normal oxygen rates, prefer to use fermentation instead of the citric acid cycle to produce ATP. For the cancer to operate normally in hypoxia, a transcription factor family is activated, known as hypoxia-induced factors (HIF), composed of a HIF-1β and a HIF-1α subunits. As HIF-1α is expressed during hypoxia, it is a great target for treatments and a breast cancer biomarker. Because of the role of HIF-1α in cancer and the high incidence of breast cancer worlwide, this review was performed in order to bring the most recent results concerning the role HIF-1α can exert in breast cancer development and progression.
The objective of this study was to evaluate the effect of aqueous extracts of Plinia cauliflora (DC.) Kausel leaves in different concentrations (0.5 to 10.0% (w/v)), on the hemostasis through changes in platelet aggregation and blood coagulation. Has been assessed by phytochemical screening (total phenols; tannins; flavonoids; alkaloids and saponins) of Plinia cauliflora (DC.) Kausel leaves using standard methodologies. The human blood by discard sample was used. The coagulation assay was carried out with 'thromboplastin hemostasis' for prothrombin time (PT) and activated partial thromboplastin time (aPTT) commercial kit, where platelets were determined by complete blood count (CBC) analyzer. The phytochemical screening showed the presence of total phenols; tannins and flavonoids. In assessing the anticoagulant activity, the aqueous extracts of P. cauliflora (DC.) Kausel leaves in different concentrations (2.0%; 2.5%; 5.0% and 10.0% (w/v) didn't show any coagulation and could not be measured on the analyzer. Hemogram (CBC) of the sample results showed a significant reduction in platelet concentration, especially in aqueous extracts 2.5%, while the other parameters did not seem to be significantly affected. Based on these preliminary results, it can be suggested that the aqueous extract of this species has anticoagulant and antiplatelet activities.
In tumor cells, higher expression of glucose transporter proteins (GLUT) and carbonic anhydrases (CAIX) genes is influenced by hypoxia-induced factors (HIF).Thus, we aimed to study the expression profile of these markers in sequential peripheral blood collections performed in breast cancer patients in order to verify their predictive potential in liquid biopsies. Gene expressions were analyzed by qPCR in tumor and blood samples from 125 patients and 25 healthy women. Differential expression was determined by the 2(−ΔCq) method. Expression of HIF-1α and GLUT1 in the blood of breast cancer patients is significantly higher (90–91 and 160–161 fold increased expression, respectively; p < 0.0001) than that found in healthy women. Their diagnostic power was confirmed by ROC curve. CAIX is also more expressed in breast cancer women blood, but its expression was detected only in a few samples. But none of these genes could be considered predictive markers. Therefore, evaluation of the expression of HIF-1α and GLUT1 in blood may be a useful laboratory tool to complement the diagnosis of breast cancer, in addition to being useful for follow-up of patients and of women with a family history of breast cancer.
AimTo evaluate alterations due to the establishment of experimental diabetes mellitus (DM) alloxan‐induced in biochemical parameters and the expression of genes MCT1, MCT4, CD147 and HIF‐1α in different tissues and in the blood profile.MethodsWistar rats (120–180g) were conditioned at the FMABC bioterium in conditions of 12 hours light/dark, climate temperature (21 ± 2 °C) and ad libitum supply of water and food. Animals of the DM group were treated with Alloxan monohydrate (120 mg/kg) intraperitoneal (ip); the control group sham (NDS) received injections of sodium chloride 0,9% (ip). The glycemic values were measured weekly during the period of treatment through a commercial glycosimeter by puncturing of the caudal vein of the animal; animals with glycemia above ≥200 mg / dL were determined as diabetic. Evaluated the biochemical parameters: glycemia, blood creatinine and urea, and the expression of molecular biomarkers in the heart, brain, kidney and blood by the RT‐qPCR technique. Data was analyzed by GraphPad Prism® 6.0, statistical differences were observed by the Mann‐Whitney test and Student T test with an established significance level in 5% (descriptive value of p <0.05).ResultsThe biochemical parameters found were: glycemia (DM7 619.1 ± 140.7 * p <0.005, n = 10 vs NDS 192.5 ± 43.64, n = 4), blood creatinine (DM7 0.46 ± 0.05 * p <0.005, n = 10 vs NDS 0.40 ± 0.07, n = 4) and urea (DM7 96.7 ± 26.6 * p <0.005, n = 10 vs. NDS 46.5 ± 7.0, n = 4) these values follow the established standards for the diabetic profile in the present study. In the molecular analyzes an increase of CD147 in the brain was observed (DM7 26.72 ± 27.45, * p <0.005, n = 9 vs NDS 1,489 ± 1,648, n = 4). In the blood profile an enhancement in the expressions of all the genes studied in the animals with DM were found; MCT1 (DM7 3,739 ± 3,057 * p <0.005, n = 10 vs NDS 0.009745 ± 0.007489, n = 4); MCT4 (DM7 7.364 ± 7.3, * p <0.005 n = 10 vs NDS 0.06399 ± 0.04844, n = 3); CD147 (DM7 4,295 ± 4,424 * p <0.005, n = 10 vs NDS 0.2212 ± 0.01653, n = 4) and HIF‐1α (DM7 1,413 ± 1,087 * p <0.005, n = 10 vs NDS 0.003833 ± 0.003741, n = 4). A positive correlation between glucose and MCT1 in the blood profile (r = 0.8061, * p <0.05, n = 10) was also noted, Spearman test.ConclusionsPreliminary data demonstrate that even early DM promotes serious biochemical changes accompanied by modifications in the expression of genes involved with glycolytic metabolism and in the cellular hypoxia mechanism. Apparently, the brain is the first tissue affected by these changes.Support or Funding InformationCAPES and CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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Diabetes mellitus is a chronic disease with prospects for an increase worldwide, therefore, researches are developed to understand its metabolic implications, as well as the early signaling of the onset of the disease and possible complications. The objective of this study was to evaluate the expression profile in the genes Mct1, Mct4, Cd147, Hif-1α and Vegffor different biological matrices in rats induced to diabetes in the determined periods of: 7, 21, 30 and 40 days. Wistar rats (160-180g, n=68), divided into shamand diabetic groups evaluated according to tissue samples from the heart, brain and kidney, blood samples; being studied in classical biochemical analysis and in the determination of intergroup differential gene expression, temporally, by qPCR. The main alterations were observed in the renal tissues - decrease in the expression of Hif-1α (21x30 days) and Vegf (21x40 days), and in the brain - with significant alterations in the evaluated genes, comparing the early group (7 days) and late groups (30 and 40 days). Thus, we observed that the evaluated genes are related to metabolic changes that, over time, corroborate the worsening of diabetes and the installation of secondary diseases, directly and/or indirectly related to the evaluated tissues.
AimThis study aimed to evaluate the potential diagnostic and/or prognostic value of VEGF and HIF 1α gene expressions in peripheral blood of patients with breast cancer under chemotherapy treatment.MethodsPeripheral blood samples and tumor biopsies were collected from 125 patients with breast cancer and from 25 healthy women (control). Blood samples were collected at diagnosis and after 3 and 6 months of the beginning of chemotherapy. Total RNA isolation was performed using TRIZol reagent. RNA was then converted to cDNA and the gene expression analysis was made by RT‐qPCR. Results were expressed as mean ± standard deviation and analysed by GraphPad Prism® 6.0 using Mann‐Withney, Friedman and Spearman tests, with a significancy level established in 5% (value of p< 0,05).ResultsGene expression analysis showed an increase of HIF 1α gene expression in patients at diagnosis when compared to that of healthy women (Patients: 0.3362 ± 0.7729, n=34 vs Donors: 0.00212 ± 0.001509, n=25, *p<0.0001). Analysis showed that in patients HIF 1α and VEGF expression is higher in peripheral blood than tumor samples (blood: 0.1927 ± 0.4754, n=108 vs Tumor: 0.09498 ± 0.2141, n=91, *p<0.0001 for HIF 1α and blood: 0.001436 ± 0.002469, n=117, Tumor: 0.002364 ± 0.007736, n=91 and *p=0.0041 for VEGF). HIF 1α also showed a differential expression along treatment (at diagnosis: 0.1432 ± 0.2161, n=102; 3 months after chemotherapy: 0.2010 ± 0.3456, n=102 and 6 months after chemotherapy: 0.1657 ± 0.2150, n=102, *p=0.0021). This differential expression along treatment was also observed for VEGF expression (at diagnosis: 0.001314 ± 0.001780, n=112; 3 months after chemotherapy: 0.001891 ± 0.002446, n=112 and 6 months after chemotherapy: 0.001674 ± 0.002260, n=112, *p<0.0001). It was found a correlation between the gene expression levels of HIF 1α and VEGF in peripheral blood (r=05881, *p<0.0001) as well as in the tumor samples (r=0.2804, *p=0.0123).ConclusionsData suggest that HIF 1α could be a diagnosis marker since there's a significant increase in its expression in blood samples from breast cancer patients when compared to healthy women. It's also observed that there's a positive correlation between VEGF and HIF 1α gene expression in peripheral blood samples.Support or Funding InformationFinancing: CNPq (process number: 133505/2018‐9) and FAPESP (Process number: 2017/03558‐3). Associated author: Carlos Henrique Foncesca Peiró Association: ASBMB (Number: 64413).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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