Functional effect of miR-1307-3p on breast cancer progression

Background: MiRNAs are non-coding RNA molecules and its function is the regulation of gene expression. In cancer, the deregulation of miRNAs allows them to act as oncogenes or tumor suppressors. From an analysis of the expression of miRNAs in breast cancer (BC) in The Cancer Genome Atlas (TCGA), it was identified that miR-1307-3p is significantly overexpressed in the tumor tissue compared to healthy tissue from patients. So far, in BC, it has only been reported that this miRNA inhibits SMYD4 and that it is involved in resistance to cisplatin through its effect on Mdm4. In this project we propose to identify the role of miR-1307-3p in proliferation, migration, invasion, angiogenesis, and possible targets involved in these processes in BC cells. Methods: RT-qPCR was used to evaluate basal levels of miR-1307-3p in the BC cell lines MDA-MB-231 and MCF-7, and the human epithelial breast MCF-10A cells. Later, we determined the effect of miR-1307-3p on proliferation, migration, and invasion in MDA-MB-231 and MCF-7, and angiogenesis in the HUVEC endothelial cells. All assays were carried out using the miR-1307-3p inhibitor. Then, nine miRNA-target prediction databases were analyzed to identify potential miR-1307-3p target genes, and their expression was analyzed by RT-qPCR in a designed 384-well plate. Finally, the targets that presented an alteration in their expression were evaluated by western blot. Results: We found that miR-1307-3p is overexpressed in MDA-MB-231 and MCF-7, compared to MCF-10A cells. We also identified that transfection with the miR-1307-3p inhibitor causes a significant decrease in the processes of proliferation, migration, invasion, and angiogenesis, when compared with untreated or negative control transfected cells. For its part, prediction databases analysis allowed us to identify 19 potential targets of miR-1307-3p. We also found that 2 genes were overexpressed, CIC and PRM2. Finally, we found an overexpression of PRM2 protein. Conclusions: MiR-1307-3p is overexpressed in BC cells. Furthermore, miR-1307-3p induces the processes of proliferation, migration and invasion in BC cells, and angiogenesis in HUVEC cells. These observations suggest that miR-1307-3p can acts as an onco-miRNA. In addition, a potential new target of miR-1307-3p was found, PRM2 which has not been previously reported in breast cancer. Further analysis to verify and validate the implication of this miR-1307-3p target are needed to understand its importance in BC

Effect of miR-660-5p in breast cancer progression

Background: Breast cancer (BC) is the most diagnosed cancer in women worldwide. MicroRNAs (miRNAs) participate in different processes of BC and their deregulation can cause them to act as oncogenes or tumor suppressors, participating in cancer progression. Using the TCGA (The Cancer Genome Atlas) database, we found that miR-660-5p significantly overexpressed and associated with poor survival in patients with this pathology. Moreover, it is reported that miR-660-5p can induce BC progression through transcription factor CP2 (TFCP2) and the downregulation of tet methylcytosine dioxygenase 2 (TET2). In this project, we propose to identify the role of miR-660-5p in proliferation, migration, invasion, angiogenesis, and the possible targets involved in these processes in BC cell lines. Methods: Basal levels of miR-660-5p were determined in BC cells MDA-MB-231 and MCF-7, and in human epithelial breast cells MCF-10A by RT-qPCR. The effect of miR-660-5p was evaluated on proliferation, migration, and invasion processes in MDA-MB-231 and MCF-7 cells. HUVEC cells were used to assess angiogenesis. All cell lines were transfected with miR-660-5p inhibitor. Analysis of nine miRNA-target prediction databases was made to identify targets of miR-660-5p. We selected the targets genes predicted by at least three of these programs, and their expression were evaluated in MDA-MB-231 cells by RT-qPCR in a customized plate. We validated those results with Western blot. Results: We found that miR-660-5p is significantly upregulated in MDA-MB-231 and MCF-7, compared to MCF-10A cells. In addition, we observed a significant decrease in proliferation, migration, and invasion in BC cells transfected with miR-660-5p inhibitor, compared to nontreated cells and miRNA inhibitor negative control cells. Similarly, we observed a significant decrease in angiogenesis of HUVEC cells transfected with miR-660-5p inhibitor. Furthermore, of all the miR-660-5p target genes identified by prediction databases, 17 were selected, and of these, three were observed upregulated and one downregulated. We found that CD8A, LIFR and TMEM41B are reported as tumor suppressors in different types of cancer. We validated those results by Western blot, observing an increase in TMEM41B protein levels in the group of cells transfected with miR-660 inhibitor compared to nontreated cells and miRNA inhibitor negative control cells. Conclusions: The results show that miR-660-5p is upregulated and involved in proliferation, migration, invasion, and angiogenesis of BC, which may lead us to suggest that this miRNA act as an onco-miRNA. In addition, we found that TMEM41B could be a potential target of miR-660-5p

Invasive Pulmonary Adenocarcinoma with Lepidic Growth Pattern in a Pregnant Patient

Among the differential diagnoses that should be considered in acute respiratory failure (ARF) are infectious processes, autoimmune diseases, interstitial pulmonary fibrosis, and pulmonary neoplasia. Timely diagnosis of lung neoplasia is complicated in the early stages. An opportune diagnosis, as well as the specific treatment, decrease mortality. ARF occurs 1 in 500 pregnancies and is most common during the postpartum period. Among the specific etiologies that cause ARF during pregnancy that must be considered are: (1) preeclampsia; (2) embolism of amniotic fluid; (3) peripartum cardiomyopathy; and (4) trophoblastic embolism. The case of a 36-year-old patient with a 33-week pregnancy and ARF is presented. The patient presented dyspnea while exerting moderate effort that progressed to orthopnea and type 1 respiratory insufficiency. Imaging studies showed bilateral alveolar infiltrates and predominantly right areas of consolidation. Blood cultures, a galactomannan assay and IgG antibodies against mycoplasma pneumoniae, were reported as negative. Autoimmune etiology was ruled out through an immunoassay. A percutaneous pulmonary biopsy was performed and an invasive pulmonary adenocarcinoma with lepidic growth pattern (i.e. lepidic pulmonary adenocarcinoma, LPA) result was reported. This etiology is rare and very difficult to recognize in acute respiratory failure cases. After infectious, autoimmune and interstitial lung fibrosis have been excluded the clinician must suspect of lung cancer in a patient with acute respiratory failure and chest imaging compatible with the presence of ground-glass nodular opacities, a solitary nodule or mass with bronchogram, and lung consolidation. In the presence of acute respiratory failure, the suspicion of pulmonary neoplasia in an adult of reproductive age must be timely. Failure to recognize this etiology can lead to fatal results

Open-Source 3D Printable GPS Tracker to Characterize the Role of Human Population Movement on Malaria Epidemiology in River Networks: A Proof-of-Concept Study in the Peruvian Amazon.

Human movement affects malaria epidemiology at multiple geographical levels; however, few studies measure the role of human movement in the Amazon Region due to the challenging conditions and cost of movement tracking technologies. We developed an open-source low-cost 3D printable GPS-tracker and used this technology in a cohort study to characterize the role of human population movement in malaria epidemiology in a rural riverine village in the Peruvian Amazon. In this pilot study of 20 participants (mean age = 40 years old), 45,980 GPS coordinates were recorded over 1 month. Characteristic movement patterns were observed relative to the infection status and occupation of the participants. Applying two analytical animal movement ecology methods, utilization distributions (UDs) and integrated step selection functions (iSSF), we showed contrasting environmental selection and space use patterns according to infection status. These data suggested an important role of human movement in the epidemiology of malaria in the Peruvian Amazon due to high connectivity between villages of the same riverine network, suggesting limitations of current community-based control strategies. We additionally demonstrate the utility of this low-cost technology with movement ecology analysis to characterize human movement in resource-poor environments

Infection and coinfection by human papillomavirus, Epstein–Barr virus and Merkel cell polyomavirus in patients with squamous cell carcinoma of the larynx: a retrospective study

Background Human papillomavirus (HPV) is recognized as an important risk factor for laryngeal carcinogenesis. Although HPV-16 and 18 have been strongly implicated, the presence of other high-risk HPV (HR-HPV) genotypes or the coinfection with Epstein-Barr virus (EBV) or Merkel cell polyomavirus (MCPV) may increase the risk, but their etiological association has not been definitively established. Methods We characterized the genotype-specific HPV and the frequency of EBV and MCPV infections through the detection of their DNA in 195 laryngeal specimens of squamous cell carcinoma (SCC) histologically confirmed. Results HPV DNA was detected in 93 (47.7%) specimens. HPV-11 was the most frequent with 68 cases (73.1%), and HPV-52 was the most frequently HR-HPV found with 51 cases, which corresponds to 54.8% of all HPV-positive specimens. EBV DNA was detected in 54 (27.7%) tumor tissue specimens of which 25 (46.3%) were in coinfection with HPV. MCPV DNA was detected only in 11 (5.6%) cases of which 5 (45.4%) were in coinfection with an HR-HPV. No association between the presence of DNA of the three examined viruses and the patient smoking habits, alcohol consumption, age, the keratinization status, differentiation grade, or localization of the tumor in the larynx were found. Discussion HPV-52 was the most prevalent HR-HPV, which may suggest that this and other genotypes in addition to HPV-16 and 18 could be considered for prophylaxis. However, further studies including non-cancer larynx cases and the evaluation of other molecular markers and viral co-infection mechanisms are needed to determine the role of the different HR-HPV genotypes, EBV, and MCPV in the etiology of SCC of the larynx

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

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