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Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited systemic treatment options. RX-5902 is a novel anti-cancer agent that inhibits phosphorylated-p68 and thus attenuates nuclear β-catenin signaling. The purpose of this study was to evaluate the ability of β-catenin signaling blockade to enhance the efficacy of anti-CTLA-4 and anti-PD-1 immune checkpoint blockade in immunocompetent, preclinical models of TNBC.
Treatment with RX-5902, anti-PD-1, anti-CTLA-4 or the combination was investigated in BALB/c mice injected with the 4 T1 TNBC cell line. Humanized BALB/c-Rag2
Il2rγ
SIRPα
(hu-CB-BRGS) mice transplanted with a human immune system were implanted with MDA-MB-231 cells. Mice were randomized into treatment groups according to human hematopoietic chimerism and treated with RX-5902, anti-PD-1 or the combination. At sacrifice, bone marrow, lymph nodes, spleen and tumors were harvested for flow cytometry analysis of human immune cells.
The addition of RX-5902 to CTLAat RX-5902 may have important immunomodulatory, as well as anti-tumor activity, in TNBC when combined with a checkpoint inhibitor.
Conclusions RX-5902 enhanced the efficacy of nivolumab in a humanized, preclinical model of TNBC. Several changes in immunologic profiles were noted in mice treated with RX-5902 and the combination, including an increase in activated TILs and a decrease in human myeloid populations, that are often associated with immunosuppression in a tumor microenvironment. RX-5902 also was shown to potentiate the effects of checkpoint inhibitors of CTLA4 and the PD-1 inhibitor in the 4 T-1 murine TNBC model. Terephthalic These findings indicate that RX-5902 may have important immunomodulatory, as well as anti-tumor activity, in TNBC when combined with a checkpoint inhibitor.
A key ethical question in genomics research relates to whether individual genetic research results should be disclosed to research participants and if so, which results are to be disclosed, by whom and when. Whilst this issue has received only scarce attention in African bioethics discourse, the extension of genomics research to the African continent has brought it into sharp focus.
In this qualitative study, we examined the views of adolescents, parents and caregivers participating in a paediatric and adolescent HIV-TB genomic study in Botswana on how solidarity and reciprocity obligations could guide decisions about feedback of individual genetic research results. Data were collected using deliberative focus group discussions and in-depth interviews.
Findings from 93 participants (44 adolescents and 49 parents and caregivers) demonstrated the importance of considering solidarity and reciprocity obligations in decisions about the return of individual genetic research results to participants. Participants viewed research participation as a mutual relationship and expressed that return of research results would be one way in which research participation could be reciprocated. They noted that when reciprocity obligations are respected, participants feel valued and not respecting reciprocity expectations could undermine participant trust and participation in future studies.
We conclude that expectations of solidarity and reciprocity could translate into an obligation to feedback selected individual genetic research results in African genomics research.
We conclude that expectations of solidarity and reciprocity could translate into an obligation to feedback selected individual genetic research results in African genomics research.
Although cardiovascular diseases in particular Pulmonary Arterial Hypertension (PAH) is associated with, high morbid-mortality in chronic hemodialysis, but its magnitude remains paradoxically unknown in sub-Saharan Africa. The aim of this study was to evaluate the prevalence of PAH and associated factors in chronic hemodialysis in Sub-Saharan African population.
In a cross-sectional study, patients treated with HD for at least 6 months in 4 hemodialysis centers were examined. PAH was defined as estimated systolic pulmonary arterial pressure (sPAP) ≥ 35 mmHg using transthoracic Doppler echocardiography performed 24 h after the HD session.
Eighty-five HD patients were included; their average age was 52.6 ± 15.9 years. Fifty-seven patients (67.1%) were male. Mean duration of HD was 13.3 ± 11 months. With reference to vascular access, 12 (14.1%), 29 (34.1%) and 44 (51.8%) patients had AVF, tunneled cuff and temporary catheter, respectively. The underlying cause of ESRD was diabetes in 30 patients (35.3%). The prevalence of PAH was 29.4%. Patients with PAH had more hyponatremia (11 (44%) vs 10 (16.7%), p = 0.010). In multivariate analysis, unsecured healthcare funding (aOR 4, 95% CI [1.18-6.018]), arrhythmia (aOR 3, 95% CI [1.29-7.34]), vascular access change (aOR 4, 95% CI [1.18-7.51]) and diastolic dysfunction (aOR 5, 95% CI [1.35-9.57] were independently associated with PAH.
One third of hemodialysis patients exhibit PAH, which is independently associated with low socioeconomic status (unsecured funding, vascular access change) and cardiovascular complications (arrhythmia, diastolic dysfunction).
One third of hemodialysis patients exhibit PAH, which is independently associated with low socioeconomic status (unsecured funding, vascular access change) and cardiovascular complications (arrhythmia, diastolic dysfunction).
Atlantoaxial fusion has been widely used for the treatment of atlantoaxial instability (AAI). However, atlantoaxial fusion sacrifices the motion of atlantoaxial articulation, and postoperative loss of cervical lordosis and aggravation of cervical kyphosis are observed. We investigated various factors under the hypothesis that the atlantodental interval (ADI) and T1 slope may be associated with sagittal alignment after atlantoaxial fusion in patients with rheumatoid arthritis (RA).
We retrospectively investigated 64 patients with RA who underwent atlantoaxial fusion due to AAI. Radiological factors, including the ADI, T1 slope, Oc-C2 angle, cervical sagittal vertical axis, and C2-C7 angle, were measured before and after surgery.
The various factors associated with atlantoaxial fusion before and after surgery were compared according to the upper and lower preoperative ADIs. There was a significant difference in the T1 slope 1year after surgery (p = 0.044) among the patients with lower preoperative ADI values.
Homepage: https://www.selleckchem.com/products/terephthalic-acid.html
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